+publisher:"Penn State University" +contributor:("John Patrick Vanden Heuvel, Committee Member")

Penn State University

1. Xu, Tongtong. Anti-Cancer Effects of Phenolic-rich Extracts of Button Mushrooms (Agaricus bisporus).

Degree: 2013, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/17505

► Standard therapies for the treatments of cancer have limitations, including lack of effectiveness against hormone-refractory tumors and toxic side-effects. Dietary anti-cancer compounds have attracted increasing… (more)

▼ Standard therapies for the treatments of cancer have limitations, including lack of effectiveness against hormone-refractory tumors and toxic side-effects. Dietary anti-cancer compounds have attracted increasing attention in cancer research because of their potential for lower toxic side effects and lower cost. Recent publications have shown that edible mushrooms are rich in phenolic compounds including simple phenolic acids and flavonoids. Given the available literature on the potential anticancer activity of phenolic compounds from other dietary sources, I hypothesized that the phenolic compounds in edible mushrooms can inhibit cancer cell growth. I compared the anti-proliferative effects of hot water, hexane, and ethyl acetate extracts of commonly consumed edible mushrooms against HT-29 human colon, H1299 lung, MCF-7 breast, and LNCaP & PC-3 prostate cancer cells using the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Brown button mushroom ethyl acetate extract (BBEA) had the most potent inhibition against cancer cell growth with LNCaP prostate cancer cells being the most sensitive (IC50 = 0.1 mg/mL after 48 h). A direct relationship was observed between total phenolic content and anti-proliferative effect of mushroom extracts. With further study, I observed that BBEA time- and dose-dependently produced reactive oxygen species in cell culture medium in both the absence or presence of prostate cancer cells over 48 h treatment period. There was also a dramatic increase in the level of intracellular ROS and DNA damage response, indicating that BBEA-induced oxidative stress may represent the mechanism of prostate cancer cell growth inhibition. I used Western blot analysis, flow cytometry, and microarray analysis to study the anti-cancer mechanism of BBEA in prostate cancer cells. Increased cleavage of caspase-3 and PARP was observed after treatment of prostate cancer cells with BBEA for 12 – 24 h, indicating induction of apoptosis. BBEA arrested prostate cancer cells at G2 phase of the cell cycle and treatment with BBEA for 12 – 24 h decreased cyclin D1, E2, A, and B1 expression in LNCaP cells compared to vehicle-treated controls. Based on microarray results, the expression of 34 genes involved in transcription regulation, cell cycle progression, DNA damage/oxidative stress response, cytoskeleton stabilization, cell proliferation, and polyamine catabolism was modified by BBEA. Finally I investigated the tumor growth inhibitory effects of brown (BBEA) and white (WBEA) button mushroom ethyl acetate extracts in LNCaP human prostate cancer cell xenograft-bearing severe combined immunodeficiency (SCID) mice. Tumor volume (mm3) and final tumor weight (g) were reduced by 18 and 22%, respectively, in mice fed a 0.5% WBEA-containing diet. By contrast, BBEA had no inhibitory effect. There was a discrepancy of growth inhibitory effect of BBEA between in vitro and in vivo models. The potential reasons for this discrepancy will be discussed. In summary, phenol-rich button mushroom extracts inhibited… Advisors/Committee Members: Joshua D Lambert, Dissertation Advisor/Co-Advisor, Robert Bruce Beelman, Committee Member, Ryan John Elias, Committee Member, John Patrick Vanden Heuvel, Committee Member.

Subjects/Keywords: Agaricus bisporus; mushrooms; cancer; phenolic compounds; apoptosis; microarray; SCID mice; xenograft tumor

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Xu, T. (2013). Anti-Cancer Effects of Phenolic-rich Extracts of Button Mushrooms (Agaricus bisporus). (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/17505

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Xu, Tongtong. “Anti-Cancer Effects of Phenolic-rich Extracts of Button Mushrooms (Agaricus bisporus).” 2013. Thesis, Penn State University. Accessed March 07, 2021. https://submit-etda.libraries.psu.edu/catalog/17505.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Xu, Tongtong. “Anti-Cancer Effects of Phenolic-rich Extracts of Button Mushrooms (Agaricus bisporus).” 2013. Web. 07 Mar 2021.

Vancouver:

Xu T. Anti-Cancer Effects of Phenolic-rich Extracts of Button Mushrooms (Agaricus bisporus). [Internet] [Thesis]. Penn State University; 2013. [cited 2021 Mar 07]. Available from: https://submit-etda.libraries.psu.edu/catalog/17505.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Xu T. Anti-Cancer Effects of Phenolic-rich Extracts of Button Mushrooms (Agaricus bisporus). [Thesis]. Penn State University; 2013. Available from: https://submit-etda.libraries.psu.edu/catalog/17505

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

2. Nilson, Mark G. Total Syntheses of the Marine Natural Products (‒)-nakadomarin A and (±)-cortistatin J via Iminium Ion Cyclizations.

Degree: 2012, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/12703

► The total synthesis of the biologically active, marine alkaloid (‒)-nakadomarin A is discussed in Part I. The key transformation in this synthesis is the stereoselective… (more)

Subjects/Keywords: total synthesis; nakadomarin; enecarbamate; Michael addition; N-acyliminium ion; metathesis; cortistatin; (4 + 3) cyclization

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APA (6^th Edition):

Nilson, M. G. (2012). Total Syntheses of the Marine Natural Products (‒)-nakadomarin A and (±)-cortistatin J via Iminium Ion Cyclizations. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/12703

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Nilson, Mark G. “Total Syntheses of the Marine Natural Products (‒)-nakadomarin A and (±)-cortistatin J via Iminium Ion Cyclizations.” 2012. Thesis, Penn State University. Accessed March 07, 2021. https://submit-etda.libraries.psu.edu/catalog/12703.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Nilson, Mark G. “Total Syntheses of the Marine Natural Products (‒)-nakadomarin A and (±)-cortistatin J via Iminium Ion Cyclizations.” 2012. Web. 07 Mar 2021.

Vancouver:

Nilson MG. Total Syntheses of the Marine Natural Products (‒)-nakadomarin A and (±)-cortistatin J via Iminium Ion Cyclizations. [Internet] [Thesis]. Penn State University; 2012. [cited 2021 Mar 07]. Available from: https://submit-etda.libraries.psu.edu/catalog/12703.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Nilson MG. Total Syntheses of the Marine Natural Products (‒)-nakadomarin A and (±)-cortistatin J via Iminium Ion Cyclizations. [Thesis]. Penn State University; 2012. Available from: https://submit-etda.libraries.psu.edu/catalog/12703

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

3. Harris, Kristina Arline. Effects of whole and refined grains on the resolution of Metabolic Syndrome and the distribution of abdominal adipose tissue in overweight and obese individuals with increased waist circumference.

Degree: 2013, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/17381

► Metabolic Syndrome (MetSyn) is a constellation of risk factors (excess abdominal adiposity, dyslipidemia, increased blood pressure, and hyperglycemia) that is due to the dysregulation of… (more)

▼ Metabolic Syndrome (MetSyn) is a constellation of risk factors (excess abdominal adiposity, dyslipidemia, increased blood pressure, and hyperglycemia) that is due to the dysregulation of insulin function and excessive abdominal adiposity. Having MetSyn increases the risk of developing type 2 diabetes and cardiovascular disease. Epidemiological studies have shown that higher whole grain intakes are associated with a lower prevalence of MetSyn or MetSyn-related biomarkers. However, there is inconsistent clinical evidence regarding the benefit of whole versus refined grains on MetSyn markers. We hypothesized that including whole grains in the place of refined grains within a healthy diet would improve MetSyn markers. A randomized, controlled, open-label, parallel study was conducted in 50 overweight and obese individuals who had or were at risk for MetSyn. Participants consumed an isocaloric diet containing either whole or refined grain products for 6 weeks followed by a hypocaloric version of the same diet for 6 weeks. All foods were provided to participants daily from a metabolic kitchen. MetSyn criteria, body composition, adipokines, endothelial function, and plasma alkylresorcinols (compliance biomarker) were measured at baseline, 6 and 12 weeks. Alkylresorcinols increased by 450% (P <0.0001) on the whole grain diet and did not change significantly on the refined grain diet, indicating that the participants were compliant to their assigned diets. Fasting plasma glucose tended to decrease more on the whole grain compared to the refined grain diet (whole: -0.24, -0.10 to -0.48 mmol/L vs. refined: -0.05, 0.06 to -0.17 mmol/L, P=0.07). Prediabetes was resolved in all participants in the whole grain group (n=9/9) and in only 13% of the refined grain group (n=1/8). Weight, waist circumference, % adipose tissue (AT; body, trunk and abdomen), cholesterol (total, LDL, and HDL), and blood pressure were decreased on both diets (P <0.05). Levels of the insulin-sensitizing adipokine, high-molecular weight adiponectin, decreased during the ISO phase in both groups (whole: -543 ± 489, vs. refined: -470 ± 718 pg/mL), but increased in the whole grain group and decreased further in the refined grain group during HYPO phase (whole: 255 ± 782, vs. refined: -106 ± 712 pg/mL, P <0.05). Similar patterns were observed with total adiponectin (P<0.05). Leptin decreased more in individuals with hyperleptinemia on the whole grain diet compared to the refined grain diet (P <0.05). Most inflammatory and oxidative stress markers and endothelial function did not change; however, a surrogate marker of arterial stiffness, the augmentation index (AI), increased in both groups (whole: 4.22 ± 14.3, vs. refined; 2.26 ± 7.29, P <0.05). In sum, the improved adipokine profile may, in part, account for the improvement in fasting glucose on the whole grain diet. Furthermore, we speculate that microbial metabolism of cereal fiber in the lower intestine may be involved in improving body insulin sensitivity, specifically through the increased… Advisors/Committee Members: Penny Margaret Kris Etherton, Dissertation Advisor/Co-Advisor, Sheila Grace West, Committee Member, John Patrick Vanden Heuvel, Committee Member, Connie Jo Rogers, Committee Member, Ryan John Elias, Special Member.

Subjects/Keywords: nutrition; weight loss; obesity; whole grain; metabolic syndrome; insulin resistance

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Harris, K. A. (2013). Effects of whole and refined grains on the resolution of Metabolic Syndrome and the distribution of abdominal adipose tissue in overweight and obese individuals with increased waist circumference. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/17381

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Harris, Kristina Arline. “Effects of whole and refined grains on the resolution of Metabolic Syndrome and the distribution of abdominal adipose tissue in overweight and obese individuals with increased waist circumference.” 2013. Thesis, Penn State University. Accessed March 07, 2021. https://submit-etda.libraries.psu.edu/catalog/17381.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Harris, Kristina Arline. “Effects of whole and refined grains on the resolution of Metabolic Syndrome and the distribution of abdominal adipose tissue in overweight and obese individuals with increased waist circumference.” 2013. Web. 07 Mar 2021.

Vancouver:

Harris KA. Effects of whole and refined grains on the resolution of Metabolic Syndrome and the distribution of abdominal adipose tissue in overweight and obese individuals with increased waist circumference. [Internet] [Thesis]. Penn State University; 2013. [cited 2021 Mar 07]. Available from: https://submit-etda.libraries.psu.edu/catalog/17381.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Harris KA. Effects of whole and refined grains on the resolution of Metabolic Syndrome and the distribution of abdominal adipose tissue in overweight and obese individuals with increased waist circumference. [Thesis]. Penn State University; 2013. Available from: https://submit-etda.libraries.psu.edu/catalog/17381

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

4. Su, Shengzhong. Transcriptional regulation of the human microsomal epoxide hydrolase gene (EPHX1) driven by a far upstream alternative promoter.

Degree: 2013, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/18909

► Microsomal epoxide hydrolase (mEH) is an important metabolizing enzyme that plays roles in both detoxification and bioactivation of xenobiotics. Human mEH gene expression is subjected… (more)

▼ Microsomal epoxide hydrolase (mEH) is an important metabolizing enzyme that plays roles in both detoxification and bioactivation of xenobiotics. Human mEH gene expression is subjected to the regulation of alternative promoter usage generating multiple transcripts, including the most prevalent, termed E1b and E1. These transcripts possess distinct untranslated first exons but encode identical mEH protein given that the second exon contains the translation initiation site. E1b is ubiquitously expressed at high levels in all tissues while E1 is selectively expressed in the liver. Although several liver-specific transcription factors were characterized previously as involved in the regulation of E1 transcription, little is known regarding the molecular mechanism regulating E1b expression. Study of those underlying processes is the principle focus of these investigations. Initially in these studies we sought to identify the key transcription factors responsible for controlling the constitutive expression of the E1b transcript. Sequence analysis of E1b proximal promoter revealed several potential Sp1/Sp3 binding sites. Site-directed mutagenesis of these motifs established their roles in regulating E1b promoter activities. Chromatin immunoprecipitation (ChIP) analyses demonstrated that both Sp1 and Sp3 are bound to the proximal promoter region of E1b. Silencing, or knockdown of Sp1 expression using siRNA had no detectable effect on the endogenous E1b transcriptional level. However, knockdown of Sp3 greatly diminished E1b expression in several different human cell lines. These results demonstrated that Sp3 in particular was involved in regulating the basal expression patterns of the mEH E1b variant transcript. Secondly, following analysis of DNase I hypersensitivity data available in the ENCODE project, we identified and characterized two intronic DNA elements in the mEH genomic region. This led to the discovery that the master oxidative stress regulator, Nuclear factor erythroid-derived 2 (NF-E2)-related factor 2 (Nrf2) functioned as a mediator of E1b upregulation in lung cancer-derived cells. Results obtained from both luciferase gene reporter and ChIP assays indicated that Nrf2 interacts with the 2nd intronic DNA element following its activation with the antioxidants, sulforaphane or tBHQ. DNA sequence analysis of the enhancer region together with electrophoretic mobility shift assays (EMSA) enabled the identification of a conserved antioxidant-response element within the enhancer that appeared to mediate these transcriptional responses. Finally in these studies, we sought to characterize differences in the transcriptional responses of the E1b and E1 promoters in hepatoma cell lines and human normal hepatocytes to chemical mediators. Nrf2 siRNA knockdown studies in hepatoma C3A cells were performed to identify the Nrf2 signaling pathway as functional in mediating the activation effects contributed by the monofunctional inducers, sulforaphane and tBHQ, to both of E1b and E1 promoters. Luciferase reporter assays… Advisors/Committee Members: Curtis John Omiecinski, Dissertation Advisor/Co-Advisor, Curtis John Omiecinski, Committee Chair/Co-Chair, Adam Bleier Glick, Committee Member, Kumble Sandeep Prabhu, Committee Member, John Patrick Vanden Heuvel, Committee Member, Joshua D Lambert, Committee Member.

Subjects/Keywords: Microsomal epoxide hydrolase; Nrf2; Xenobiotic metabolism; Bioactivation; Lung cancer; Sp1; Sp3; AhR

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Su, S. (2013). Transcriptional regulation of the human microsomal epoxide hydrolase gene (EPHX1) driven by a far upstream alternative promoter. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/18909

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Su, Shengzhong. “Transcriptional regulation of the human microsomal epoxide hydrolase gene (EPHX1) driven by a far upstream alternative promoter.” 2013. Thesis, Penn State University. Accessed March 07, 2021. https://submit-etda.libraries.psu.edu/catalog/18909.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Su, Shengzhong. “Transcriptional regulation of the human microsomal epoxide hydrolase gene (EPHX1) driven by a far upstream alternative promoter.” 2013. Web. 07 Mar 2021.

Vancouver:

Su S. Transcriptional regulation of the human microsomal epoxide hydrolase gene (EPHX1) driven by a far upstream alternative promoter. [Internet] [Thesis]. Penn State University; 2013. [cited 2021 Mar 07]. Available from: https://submit-etda.libraries.psu.edu/catalog/18909.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Su S. Transcriptional regulation of the human microsomal epoxide hydrolase gene (EPHX1) driven by a far upstream alternative promoter. [Thesis]. Penn State University; 2013. Available from: https://submit-etda.libraries.psu.edu/catalog/18909

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

5. Kapelewski, Christine Halina. Effects of age on nicotine consumption and enzyme activity following methoxsalen administration in C57BL/6J male mice .

Degree: 2011, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/11623

► With tobacco use and nicotine addiction reaching epidemic proportions worldwide, the race to find effective smoking cessation aids and methods for all populations of individuals… (more)

▼ With tobacco use and nicotine addiction reaching epidemic proportions worldwide, the race to find effective smoking cessation aids and methods for all populations of individuals is in full swing. There are several drugs on the market today specific for this purpose; however, many of these pharmacotherapies are not universally helpful, particularly for adolescents. Age, along with interindividual genetic polymorphisms in the enzyme responsible for nicotine metabolism (CYP2A6), may contribute to these disparities. Mimicking the genetic variants of this enzyme with known CYP2A6 inhibitors (e.g., methoxsalen) in adolescents and adults could provide crucial evidence for the role of these biological and genetic influences on cigarette consumption and nicotine dependence. This dissertation is aimed to understand the effects of age on nicotine consumption and metabolism following acute and chronic methoxsalen administration in adolescent and adult male C57BL/6J mice. Experiment I was a 1-day study in which adolescent (n=60) and adult (n=60) male C57BL/6J mice received either no injection or a single subcutaneous injection of either physiological saline, vehicle (Emulphor, distilled water and ethyl alcohol) or one of two doses of methoxsalen (5 or 10 mg/kg), followed by access to a 3-bottle oral nicotine paradigm [tap water, 50 (LOW NIC) and 200 (HIGH NIC) ug/ml (-)-freebase nicotine dissolved in tap water] for 12 hours. To further investigate the age differences in nicotine consumption and drug effects on serum cotinine (ng/ml/g), an 8-day two-phase study with adolescent (n=32) and adult (n=32) male C57BL/6J mice (Experiment II) was conducted. For the first four days (Phase I), animals received 24-hour unlimited access to the 3-bottle oral nicotine iii paradigm (tap water, LOW NIC and HIGH NIC). During the four days of Phase II, animals continued to have access to the water and nicotine bottles, but were also given daily subcutaneous injections of either vehicle or 10 mg/kg 8MOP at the end of the light cycle. For Experiment I and II, nicotine exposure continued until sacrifice when livers were removed and trunk blood was collected to assess hepatic CYP2a5 and CYP2e1 gene expression and serum cotinine levels, respectively. In Experiment I, adults consumed more nicotine (mL, mg/kg, % total fluid intake) than did adolescents, regardless of drug treatment. Results for Experiment II regarding nicotine consumption were not conclusive. For both studies, however, methoxsalen was found to be an age-dependent CYP2a5 inhibitor, such that serum cotinine levels (ng/ml/g) were reduced with increasing dosages of methoxsalen in adults, but not adolescents. Drug treatment and age did not alter relative gene expression levels for CYP2a5 or CYP2e1. Results of these two experiments provide significant contributions to the small pool of scientific literature regarding the effects of methoxsalen on nicotine consumption and pharmacokinetics in mouse models. Alternative methods for future studies that are indicated below are necessary to test… Advisors/Committee Members: Laura Klein, Dissertation Advisor/Co-Advisor, Laura Klein, Committee Chair/Co-Chair, Steven A Branstetter, Committee Member, David John Vandenbergh, Committee Member, John Patrick Vanden Heuvel, Committee Member.

Subjects/Keywords: methoxsalen; mouse; smoking cessation; nicotine; adolescent; CYP2a5

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Kapelewski, C. H. (2011). Effects of age on nicotine consumption and enzyme activity following methoxsalen administration in C57BL/6J male mice . (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/11623

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Kapelewski, Christine Halina. “Effects of age on nicotine consumption and enzyme activity following methoxsalen administration in C57BL/6J male mice .” 2011. Thesis, Penn State University. Accessed March 07, 2021. https://submit-etda.libraries.psu.edu/catalog/11623.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Kapelewski, Christine Halina. “Effects of age on nicotine consumption and enzyme activity following methoxsalen administration in C57BL/6J male mice .” 2011. Web. 07 Mar 2021.

Vancouver:

Kapelewski CH. Effects of age on nicotine consumption and enzyme activity following methoxsalen administration in C57BL/6J male mice . [Internet] [Thesis]. Penn State University; 2011. [cited 2021 Mar 07]. Available from: https://submit-etda.libraries.psu.edu/catalog/11623.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Kapelewski CH. Effects of age on nicotine consumption and enzyme activity following methoxsalen administration in C57BL/6J male mice . [Thesis]. Penn State University; 2011. Available from: https://submit-etda.libraries.psu.edu/catalog/11623

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

6. Roussell, Michael A. THE EFFECTS OF A DIET RICH IN LEAN BEEF ON MULTIPLE RISK FACTORS FOR CARDIOVASCULAR DISEASE: THE BEEF IN AN OPTIMAL LEAN DIET (BOLD) STUDY .

Degree: 2011, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/11770

► Background: Beef often is excluded in cholesterol-lowering diets as a means of controlling saturated fatty acids (SFA). However, the effects of a dietary pattern that… (more)

▼ Background: Beef often is excluded in cholesterol-lowering diets as a means of controlling saturated fatty acids (SFA). However, the effects of a dietary pattern that meets dietary recommendations for SFA (<7% calories) and includes lean beef on cardiovascular disease (CVD) risk factors have not been evaluated. Objective: To examine the effects of a cholesterol-lowering diet containing lean beef (BOLD 4.0 oz/d; BOLD+ 5.4 oz/d) on low density lipoprotein cholesterol (LDL-C), and compare these effects to an Average American Diet (AAD). Design: Thirty six moderately hypercholesterolemic individuals (LDL-C >110 mg/dL) completed a randomized crossover controlled feeding study. Participants were fed 4 interventions diets; AAD [33% total fat, 12% SFA, 49% carbohydrate (CHO), 19% protein (PRO), 0.7 oz beef/d], DASH (27% total fat, 6% SFA, 50% CHO, 19% PRO, 1.0oz beef/d), BOLD (28% total fat, 6% SFA, 54% CHO, 19% PRO, 4.0 oz beef/d), and BOLD+ (28% total fat, 6% SFA, 46% CHO, 28% PRO, 5.4 oz beef/d) for five weeks with a 1 week washout between diets. Lipids, lipoproteins, apolipoproteins, blood pressure (BP), blood vessel function, C-Reactive Protein (CRP), Heme oxgense-1 (HO-1) were measured at the beginning of the intervention and at the end of each diet period. Equations were developed to predict TG and high density lipoprotein cholesterol (HDL-C) changes from AAD based on changes in food group intakes (recommended by MyPyramid.gov and the DASH diet) between DASH, BOLD, BOLD+ and AAD. Results: There were significant reductions (p<0.05) in total cholesterol (TC) and LDL-C in response to the DASH (-19.0 ±4.3 and -14.4 ±3.7 mg/dL), BOLD (-18.6 ±4.1 and -13.5 ±3.6 mg/dL), and BOLD+ (-19.6±4.1 and -13.5 ±3.8 mg/dL) diets versus the AAD (-8.5 ±4.1 and -5.5 ±3.9 mg/dL). Systolic BP (SBP) was only significantly reduced following the BOLD+ diet compared to AAD (-4.24 mm Hg). Significant reductions also were observed for Apo A1, Apo C-III, and Apo C-III bound to Apo A1 particles following the BOLD and BOLD+ (p<0.05) compared to AAD. Arterial stiffness was reduced following the BOLD (10.37 ± 3.0%) diet compared to AAD (14.47 ± 3.6%), with no other changes in vascular function. There were no significant differences between the HDL-C changes predicted using previously validated equations, and the MyPyramid.gov food group model or the DASH diet food group model. HO-1 levels remained unchanged throughout the intervention. No significant changes were observed in relative gene expression of HO-1, monocyte chemotactic protein-1, chemokine (C-C motif) receptor 2, gp91phox, or Biliverdin IXα reductase mRNA in response to the dietary treatments. Conclusions: In conclusion, lean beef can be included in a cholesterol-lowering diet that is controlled for SFA; this dietary pattern elicits reductions in TC and LDL-C that are equivalent to heart-healthy plant protein-rich diets, such as the DASH diet. In addition, increasing total dietary protein by including lean beef and other animal proteins also is an effective… Advisors/Committee Members: Penny Margaret Kris Etherton, Dissertation Advisor/Co-Advisor, Penny Margaret Kris Etherton, Committee Chair/Co-Chair, Trent Gaugler, Committee Member, Sheila Grace West, Committee Member, Peter Gillies, Committee Member, John Patrick Vanden Heuvel, Committee Member.

Subjects/Keywords: lean beef; saturated fat; cardiovascular disease; nutrition; red meat

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Roussell, M. A. (2011). THE EFFECTS OF A DIET RICH IN LEAN BEEF ON MULTIPLE RISK FACTORS FOR CARDIOVASCULAR DISEASE: THE BEEF IN AN OPTIMAL LEAN DIET (BOLD) STUDY . (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/11770

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Roussell, Michael A. “THE EFFECTS OF A DIET RICH IN LEAN BEEF ON MULTIPLE RISK FACTORS FOR CARDIOVASCULAR DISEASE: THE BEEF IN AN OPTIMAL LEAN DIET (BOLD) STUDY .” 2011. Thesis, Penn State University. Accessed March 07, 2021. https://submit-etda.libraries.psu.edu/catalog/11770.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Roussell, Michael A. “THE EFFECTS OF A DIET RICH IN LEAN BEEF ON MULTIPLE RISK FACTORS FOR CARDIOVASCULAR DISEASE: THE BEEF IN AN OPTIMAL LEAN DIET (BOLD) STUDY .” 2011. Web. 07 Mar 2021.

Vancouver:

Roussell MA. THE EFFECTS OF A DIET RICH IN LEAN BEEF ON MULTIPLE RISK FACTORS FOR CARDIOVASCULAR DISEASE: THE BEEF IN AN OPTIMAL LEAN DIET (BOLD) STUDY . [Internet] [Thesis]. Penn State University; 2011. [cited 2021 Mar 07]. Available from: https://submit-etda.libraries.psu.edu/catalog/11770.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Roussell MA. THE EFFECTS OF A DIET RICH IN LEAN BEEF ON MULTIPLE RISK FACTORS FOR CARDIOVASCULAR DISEASE: THE BEEF IN AN OPTIMAL LEAN DIET (BOLD) STUDY . [Thesis]. Penn State University; 2011. Available from: https://submit-etda.libraries.psu.edu/catalog/11770

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

7. Hogan, Kelly A. MODULATION OF NUCLEAR FACTOR KAPPA B (NFκB) TRANSACTIVATION BY TRANSFORMING GROWTH FACTOR β-1 (TGFβ-1) IN KERATINOCYTES: IMPLICATIONS FOR RESPONSIVENESS TO ULTRAVIOLET RADIATION (UVB) .

Degree: 2011, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/12539

► Molecular crosstalk leading to the integration of signal transduction pathways—and the formation of a signaling network—is particularly important for maintaining cellular homeostasis. Stimuli received at… (more)

▼ Molecular crosstalk leading to the integration of signal transduction pathways—and the formation of a signaling network—is particularly important for maintaining cellular homeostasis. Stimuli received at the cell surface and transduced to the nucleus can expect to be modified by any number of inputs in a highly context-dependent and cell-specific manner. Nuclear factor kappa B (NFκB) and transforming growth factor β-1 (TGFβ-1) are not only critical factors mediating inflammation, but they also play a substantial role in cancer progression. Therefore, understanding the intersection of these factors may shed light on inflammatory diseases and progression of cancer in skin. However, little is known about how TGFβ-1 and NFκB interact in keratinocytes, which rely heavily on both factors to maintain homeostasis. These studies provide data in keratinocytes that suggest TGFβ-1 modulated NFκB-dependent expression of proinflammatory cytokines, namely TNFα. Although results in these studies fail to show TGFβ-1-mediated activation of upstream molecules of the canonical NFκB pathway or translocation of NFκB, preliminary evidence reveals that TGFβ-1 activating kinase (TAK-1) may provide a molecular link between TGFβ-1 receptor activation and NFκB transactivation. In spite of the fact that upstream signaling events are only speculative and part of ongoing inquiry, results presented in this chapter support the hypothesis that TGFβ-1-mediated NFκB transactivation of gene expression is Smad3-dependent. Furthermore, TGFβ-1 potentiates NFκB binding to consensus DNA sites, which putatively involves both the p50 and p65 subunit. The biological relevance of TGFβ-1 and NFκB crosstalk leading to expression of proinflammatory cytokines is also explored. Preliminary evidence suggests that this pathway may have a role in TGFβ-1-mediated apoptosis, differentiation, and ras-mediated induction of NFκB-dependent genes in keratinocytes. These studies are the first to show an intersection between TGFβ-1 and NFκB pathways, which may represent a mechanism by which TGFβ-1 ‘tunes’ or modulates NFκB-dependent gene expression. The biological relevance of TGFβ-1-mediated TNFα was then explored in the context of ultraviolet radiation responsiveness, which elicits an inflammatory response involving the proinflammatory cytokine TNFα. Ultraviolet radiation, particularly the UVB wavelengths ranging from 280-320 nm, is a whole carcinogen capable of initiating and promoting squamous cell carcinoma (SCC), among other types of skin cancer, in both humans and laboratory rodents after repeated UVB exposure over time. Responsiveness to UVB, specifically, has not been particularly well-characterized in keratinocytes. Presently, the literature reflects more rigorous characterization of the UVC wavelengths in cell types that are typically not sun-exposed. Furthermore, published studies using the mouse as a model… Advisors/Committee Members: Adam Glick Ph D, Dissertation Advisor/Co-Advisor, Adam Bleier Glick, Committee Chair/Co-Chair, John Patrick Vanden Heuvel, Committee Member, Kumble Sandeep Prabhu, Committee Member, Andrea Marie Mastro, Committee Member, Avery August, Committee Member, Peter John Hudson, Committee Member.

Subjects/Keywords: TGF beta-1; ultraviolet radiation; NF kappa B; keratinocytes; TNF alpha; skin

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Hogan, K. A. (2011). MODULATION OF NUCLEAR FACTOR KAPPA B (NFκB) TRANSACTIVATION BY TRANSFORMING GROWTH FACTOR β-1 (TGFβ-1) IN KERATINOCYTES: IMPLICATIONS FOR RESPONSIVENESS TO ULTRAVIOLET RADIATION (UVB) . (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/12539

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Hogan, Kelly A. “MODULATION OF NUCLEAR FACTOR KAPPA B (NFκB) TRANSACTIVATION BY TRANSFORMING GROWTH FACTOR β-1 (TGFβ-1) IN KERATINOCYTES: IMPLICATIONS FOR RESPONSIVENESS TO ULTRAVIOLET RADIATION (UVB) .” 2011. Thesis, Penn State University. Accessed March 07, 2021. https://submit-etda.libraries.psu.edu/catalog/12539.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Hogan, Kelly A. “MODULATION OF NUCLEAR FACTOR KAPPA B (NFκB) TRANSACTIVATION BY TRANSFORMING GROWTH FACTOR β-1 (TGFβ-1) IN KERATINOCYTES: IMPLICATIONS FOR RESPONSIVENESS TO ULTRAVIOLET RADIATION (UVB) .” 2011. Web. 07 Mar 2021.

Vancouver:

Hogan KA. MODULATION OF NUCLEAR FACTOR KAPPA B (NFκB) TRANSACTIVATION BY TRANSFORMING GROWTH FACTOR β-1 (TGFβ-1) IN KERATINOCYTES: IMPLICATIONS FOR RESPONSIVENESS TO ULTRAVIOLET RADIATION (UVB) . [Internet] [Thesis]. Penn State University; 2011. [cited 2021 Mar 07]. Available from: https://submit-etda.libraries.psu.edu/catalog/12539.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Hogan KA. MODULATION OF NUCLEAR FACTOR KAPPA B (NFκB) TRANSACTIVATION BY TRANSFORMING GROWTH FACTOR β-1 (TGFβ-1) IN KERATINOCYTES: IMPLICATIONS FOR RESPONSIVENESS TO ULTRAVIOLET RADIATION (UVB) . [Thesis]. Penn State University; 2011. Available from: https://submit-etda.libraries.psu.edu/catalog/12539

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

8. Skulas-Ray, Ann Christine. NUTRITION INTERVENTIONS FOR IMPROVING CARDIOVASCULAR DISEASE RISK FACTORS.

Degree: 2011, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/11707

► This dissertation investigated the effects of high antioxidant spices and omega-3 fatty acids on cardiovascular risk factors. The unifying theme of these studies is adding… (more)

Subjects/Keywords: omega-3; spices; cardiovascular; triglycerides; fish; antioxidant

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Skulas-Ray, A. C. (2011). NUTRITION INTERVENTIONS FOR IMPROVING CARDIOVASCULAR DISEASE RISK FACTORS. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/11707

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Skulas-Ray, Ann Christine. “NUTRITION INTERVENTIONS FOR IMPROVING CARDIOVASCULAR DISEASE RISK FACTORS.” 2011. Thesis, Penn State University. Accessed March 07, 2021. https://submit-etda.libraries.psu.edu/catalog/11707.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Skulas-Ray, Ann Christine. “NUTRITION INTERVENTIONS FOR IMPROVING CARDIOVASCULAR DISEASE RISK FACTORS.” 2011. Web. 07 Mar 2021.

Vancouver:

Skulas-Ray AC. NUTRITION INTERVENTIONS FOR IMPROVING CARDIOVASCULAR DISEASE RISK FACTORS. [Internet] [Thesis]. Penn State University; 2011. [cited 2021 Mar 07]. Available from: https://submit-etda.libraries.psu.edu/catalog/11707.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Skulas-Ray AC. NUTRITION INTERVENTIONS FOR IMPROVING CARDIOVASCULAR DISEASE RISK FACTORS. [Thesis]. Penn State University; 2011. Available from: https://submit-etda.libraries.psu.edu/catalog/11707

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

9. Arner, Ryan Jason. MYO-INOSITOL OXYGENASE: MOLECULAR ENZYMOLOGY AND TISSUE SPECIFIC EXPRESSION.

Degree: 2008, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/5928

► myo-Inositol (MI) and its various biochemical derivatives are very widely distributed in mammalian tissues, higher plants, fungi and some bacteria where they play an important… (more)

▼ myo-Inositol (MI) and its various biochemical derivatives are very widely distributed in mammalian tissues, higher plants, fungi and some bacteria where they play an important role in many aspects of cellular regulation including membrane structure, signal transduction and osmoregulation (Holub, 1986;Majerus, 1992;Loewus and Loewus, 1983). The first committed step in the metabolism of MI occurs predominantly in the kidney and involves the oxidative cleavage of the ring to give D-glucuronic acid (Howard and Anderson, 1967;Charalampous and Lyras, 1957). This reaction is catalyzed by the enzyme myo-inositol oxygenase (EC 1.13.99.1, MIOX). In order to generate sufficient pure enzyme for mechanistic study, as well as to clarify the discrepancies of past research, a porcine MIOX clone was generated and expressed in a bacterial system. A full-length cDNA was isolated from a porcine kidney library with an open reading frame of 849 bp and a corresponding protein subunit molecular mass of 32.7 kDa. The cDNA was expressed in a bacterial pET expression system and an active recombinant MIOX was purified from bacterial lysates to electrophoretic homogeneity. The purified enzyme displayed the same catalytic properties as the native enzyme with Km and kcat values of 5.9 mM and 11 min-1, respectively. The pI value was estimated to be 4.5. Preincubation with 1 mM Fe2+ and 2 mM cysteine was essential for the enzyme activity. D-chiro-inositol, a myo-inositol isomer, is a substrate for the rMIOX with an estimated Km of 33.5 mM. Both myo-inositol and D-chiro-inositol have been implicated in the pathogenesis of diabetes. Previously the native MIOX enzyme was reported to be likely found in a complex with the enzyme responsible for the second step of MI catabolism, i.e. glucuronate reductase (Reddy et al., 1981a), which is also known as aldehyde reductase or ALR1 (EC 1.1.1.2) (De Jongh et al., 1987). The MIOX:ALR1 complex was partially purified and the activity examined. MIOX activity was present without reactivation with Fe/Cys, as is required with pure MIOX. When inositol is supplied to the complex as substrate, activity can be detected by the consumption of NADPH by the reductase. Adding similar concentrations of free glucuronate as that produced by the MIOX activity resulted in no detectable activity, indicating the ALR1 was trapping acyclic glucuronate from MIOX. However, no activity was detected with inositol as substrate when the aldose reductase inhibitor Sorbinil was added at 10µM. The same concentration inhibited pure ALR1 by 90% when glucuronate was the substrate. No inhibition of recombinant MIOX by Sorbinil was observed. These results suggest the possibility that aldose reductase inhibitor treatment for diabetes complications may have an impact on the inositol catabolic pathway. In order to study the physiological relevance of the MIOX:ALR1 complex, the expression pattern of MIOX must be established. The expression pattern of MIOX in hog tissues was examined by Western blot, Northern blot, and RT-PCR methods. … Advisors/Committee Members: Ming Tien, Committee Member, Avery August, Committee Member, Madhu Reddy, Committee Chair/Co-Chair, John Patrick Vanden Heuvel, Committee Member.

Subjects/Keywords: mono-oxygenase; kidney; d-glucuronate; diabetes

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Arner, R. J. (2008). MYO-INOSITOL OXYGENASE: MOLECULAR ENZYMOLOGY AND TISSUE SPECIFIC EXPRESSION. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/5928

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Arner, Ryan Jason. “MYO-INOSITOL OXYGENASE: MOLECULAR ENZYMOLOGY AND TISSUE SPECIFIC EXPRESSION.” 2008. Thesis, Penn State University. Accessed March 07, 2021. https://submit-etda.libraries.psu.edu/catalog/5928.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Arner, Ryan Jason. “MYO-INOSITOL OXYGENASE: MOLECULAR ENZYMOLOGY AND TISSUE SPECIFIC EXPRESSION.” 2008. Web. 07 Mar 2021.

Vancouver:

Arner RJ. MYO-INOSITOL OXYGENASE: MOLECULAR ENZYMOLOGY AND TISSUE SPECIFIC EXPRESSION. [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Mar 07]. Available from: https://submit-etda.libraries.psu.edu/catalog/5928.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Arner RJ. MYO-INOSITOL OXYGENASE: MOLECULAR ENZYMOLOGY AND TISSUE SPECIFIC EXPRESSION. [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/5928

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

10. Mercer, Robyn R. BONE-METASTATIC BREAST CANCER CELLS INHIBIT OSTEOBLAST FUNCTION.

Degree: 2008, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/6495

► ABSTRACT Breast cancer frequently metastasizes to bone, resulting in osteolytic lesions. These lesions, formed by stimulated osteoclasts, cause pain, an increased susceptibility to fractures, and… (more)

▼ ABSTRACT Breast cancer frequently metastasizes to bone, resulting in osteolytic lesions. These lesions, formed by stimulated osteoclasts, cause pain, an increased susceptibility to fractures, and hypercalcemia. It has been shown that breast cancer cells communicate with osteoblasts and subsequently stimulate osteoclast activity; however, little research has focused on understanding the interaction between breast cancer cells and osteoblasts. To study how cancer cells affect osteoblasts, MC3T3-E1 cells, an immature osteoblast cell line that differentiates in vitro, were cultured with conditioned medium from MDA-MB-231 cells, a bone-metastatic breast cancer cell line. We determined that alkaline phosphatase activity and mineralization, two defining characteristics of a mature osteoblast, were blocked. Moreover, mRNA expression for both bone sialoprotein and osteocalcin, two genes upregulated during osteoblast differentiation, were not expressed even after 25 days of culture. Together, these data suggested that when cultured with MDA-MB-231 conditioned medium, MC3T3-E1 cells did not differentiate into mature osteoblasts. We speculated that the conditioned medium factor causing this inhibition in differentiation was transforming growth factor beta (TGFbeta). To test this, MDA-MB-231 conditioned medium was pretreated with a neutralizing antibody to TGFbeta. The neutralized conditioned medium was then added to MC3T3-E1 osteoblasts. RNA expression of alkaline phosphatase, bone sialoprotein, and osteocalcin were all restored in the presence of TGFbeta-neutralized conditioned medium. While trying to understand how breast cancer conditioned medium affected osteoblast differentiation, we made another key observation: MDA-MB-231 conditioned medium altered MC3T3-E1 morphology and adhesion. Examination with interference reflection microscopy revealed that MC3T3-E1 osteoblasts had fewer focal adhesion plaques when cultured with MDA-MB-231 conditioned medium. Further scrutiny revealed a substantial alteration in actin stress fibers. Instead of forming normal stress fibers, cells cultured with MDA-MB-231 conditioned medium demonstrated thick cortical filaments, as well as areas of large, punctate staining. MDA-MB-231 conditioned medium contains many factors, including platelet derived growth factor (PDGF), insulin-like growth factor (IGF), and TGFbeta. Because each of these factors are capable of reorganizing actin stress fibers and altering cell adhesion, MDA-MB-231 conditioned medium was treated with neutralizing antibodies to them. MC3T3-E1 osteoblasts were then cultured with the neutralized conditioned medium and assayed for changes in adhesion. Only when all three cytokines were neutralized was there a restoration in actin stress fiber formation and in focal adhesion plaques. To date, research in the field has focused on finding ways to inhibit osteoclast activity in an effort to curb bone loss. While this is an important approach, the information obtained from our study indicates that the osteoblast… Advisors/Committee Members: Andrea Marie Mastro, Committee Chair/Co-Chair, Andrew Thomas Henderson, Committee Member, Richard John Frisque, Committee Member, John Patrick Vanden Heuvel, Committee Member, Carol V Gay, Committee Member.

Subjects/Keywords: breast cancer; osteoblast; metastasis; bone

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Mercer, R. R. (2008). BONE-METASTATIC BREAST CANCER CELLS INHIBIT OSTEOBLAST FUNCTION. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/6495

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Mercer, Robyn R. “BONE-METASTATIC BREAST CANCER CELLS INHIBIT OSTEOBLAST FUNCTION.” 2008. Thesis, Penn State University. Accessed March 07, 2021. https://submit-etda.libraries.psu.edu/catalog/6495.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Mercer, Robyn R. “BONE-METASTATIC BREAST CANCER CELLS INHIBIT OSTEOBLAST FUNCTION.” 2008. Web. 07 Mar 2021.

Vancouver:

Mercer RR. BONE-METASTATIC BREAST CANCER CELLS INHIBIT OSTEOBLAST FUNCTION. [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Mar 07]. Available from: https://submit-etda.libraries.psu.edu/catalog/6495.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Mercer RR. BONE-METASTATIC BREAST CANCER CELLS INHIBIT OSTEOBLAST FUNCTION. [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/6495

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

11. Chiaro, Christopher Richard. Identification of Endogenous Modulators for the Aryl Hydrocarbon Receptor .

Degree: 2008, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/8032

► The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor capable of being regulated by a structurally diverse array of chemicals ranging from environmental carcinogens… (more)

▼ The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor capable of being regulated by a structurally diverse array of chemicals ranging from environmental carcinogens to dietary metabolites. A member of the basic helix-loop-helix/ Per-Arnt-Sim (bHLH-PAS) super-family of DNA binding regulatory proteins, the AhR is an important developmental regulator that can be detected in nearly all mammalian tissues. Prior to ligand activation, the AhR resides in the cytosol as part of an inactive oligomeric protein complex comprised of the AhR ligand-binding subunit, a dimer of the 90 kDa heat shock protein, and a single molecule each of the immunophilin like X-associated protein 2 (XAP2) and p23 proteins. Functioning as chemosensor, the AhR responds to both endobiotic and xenobiotic derived chemical ligands by ultimately directing the expression of metabolically important target genes. Primarily responsible for mediating the toxicological and biological effects of dioxin and other environmentally persistent carcinogens, the AhR was originally characterized for its role in orchestrating the adaptive metabolic response to xenobiotic compounds. Recently, however, the AhR has been identified as performing a critical role in a number of physiologically important life functions, including proper embryonic and liver development, immune system homeostasis, resolution of fetal vasculature, and maintenance of normal cardiac physiology. Currently, the most potent AhR agonists to be identified are of synthetic origin, yet an increasing number of natural compounds have been shown to activate the receptor. Although essential roles for the AhR in normal cellular biology have already been established and continue to evolve, no high affinity physiologically relevant endogenous ligand has been identified. Therefore, the ultimate goal of this research project was to identify such ligands. The initial data presented in this thesis confirms the presence of a putative endogenous ligand(s) for the AhR in the CV-1 cell line, while demonstrating the existence of an AhR regulated feedback mechanism functioning to control putative endogenous ligand levels. Derived from the kidney epithelium of the African green monkey, the CV-1 cell line is an immortalized cell culture line exhibiting minimal AhR expression. Consequentially, the level of AhR-regulated cytochrome P450 metabolism is also compromised allowing for subsequent accumulation of cellular metabolites, including potential intracellular endogenous ligands for the AhR. However, the ectopic expression of AhR-regulated cytochrome P450s from the 1A or 1B families effectively reduced the high level of constitutive AhR activity observed in CV-1 cells. Meanwhile cytochrome P450 2E1, an isoform not regulated by AhR, exhibited no significant effect. Furthermore, extracts of lung tissue prepared from Ahr-null mice clearly revealed, by the increased AhR activation potential compared to “wild-type” mice, the accumulation of an endogenous ligand for the AhR. Coupled with the… Advisors/Committee Members: Gary H Perdew, Committee Chair/Co-Chair, Madhu Reddy, Committee Member, A Daniel Jones, Committee Member, John Patrick Vanden Heuvel, Committee Member.

Subjects/Keywords: leukotrienes; eicosanoids; dioxins; TCDD; AhR; DiHETEs; HETEs

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Chiaro, C. R. (2008). Identification of Endogenous Modulators for the Aryl Hydrocarbon Receptor . (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/8032

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Chiaro, Christopher Richard. “Identification of Endogenous Modulators for the Aryl Hydrocarbon Receptor .” 2008. Thesis, Penn State University. Accessed March 07, 2021. https://submit-etda.libraries.psu.edu/catalog/8032.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Chiaro, Christopher Richard. “Identification of Endogenous Modulators for the Aryl Hydrocarbon Receptor .” 2008. Web. 07 Mar 2021.

Vancouver:

Chiaro CR. Identification of Endogenous Modulators for the Aryl Hydrocarbon Receptor . [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Mar 07]. Available from: https://submit-etda.libraries.psu.edu/catalog/8032.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Chiaro CR. Identification of Endogenous Modulators for the Aryl Hydrocarbon Receptor . [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/8032

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

12. Vunta, Hema Latha. Redox regulation of the NF-kappaB pathway in macrophages: Role of 15-Deoxy-delta 12,14-prostaglandin J2.

Degree: 2008, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/8266

► Redox-based regulation of gene expression has emerged as a fundamental regulatory mechanism in cell biology. It is increasingly clear that over-production of reactive oxygen species… (more)

▼ Redox-based regulation of gene expression has emerged as a fundamental regulatory mechanism in cell biology. It is increasingly clear that over-production of reactive oxygen species (ROS) by immune cells, resulting in oxidative stress, plays a prominent role in several disease states, including cardiovascular diseases, arthritis, cancer, and AIDS. Of particular importance is the oxidative stress induced over-expression of cyclooxygenase (COX)-2 that is characteristic of inadequate selenium (Se) nutrition. Clinical trials and epidemiological studies have strongly suggested the beneficial effects of Se supplementation in prevention and/or treatment of some of these diseases. To understand the molecular mechanisms underlying the anti-inflammatory property of Se, the RAW 264.7 macrophage cell line or bone marrow macrophages (BMDM) isolated from mice on Se-deficient or Se-supplemented diets were cultured in media deficient or supplemented with Se. In vitro kinase assays revealed that Se-supplementation decreased the activity of IkappaB kinase (IKK) ƒÒ in bacterial lipopolysaccharide (LPS)-treated macrophages. Stimulation by LPS of Se-supplemented macrophages resulted in a time-dependent increase in 15-deoxy- ƒ´12, 14-prostaglandin J2 (15d-PGJ2) formation, an endogenous inhibitor of IKKƒÒ activity. Further analysis revealed that inhibition of IKKƒÒ activity in Se-supplemented cells correlated with the Michael addition product of 15d-PGJ2 with Cys-179 of IKKƒÒ, while the formation of such an adduct was significantly decreased in the Se-deficient macrophages. In addition, anti-inflammatory activities of Se were also mediated by the 15d-PGJ2-dependent activation of the PPARƒ× in macrophages. Experiments using specific COX inhibitors and genetic knockdown approaches indicated that the COX-1, and not the COX-2 pathway, was responsible for the increased synthesis of 15d-PGJ2 in Se-supplemented macrophages. Se-supplementation also led to the decrease of the expression of mPGES-1 and TXS; while the expression of H-PGDS was significantly increased. The results presented here argue that incorporation of Se into selenoproteins causes the shunting of arachidonic acid towards 15d-PGJ2 production, which further acts in a positive feedback loop via the activation of PPARƒ×-dependent transcription of H-PGDS to cause a significant shift in the metabolism of the arachidonic acid by the COX pathway towards 15d-PGJ2 rather than the pro-inflammatory PGE2. In conclusion, these results suggest that Se-supplementation protects macrophages against oxidative stress-induced pro-inflammatory gene expression via shunting arachidonic acid metabolism towards 15d-PGJ2, while COX-1 is an important enzyme in the production of 15d-PGJ2. Advisors/Committee Members: Kumble Sandeep Prabhu, Committee Chair/Co-Chair, Madhu Reddy, Committee Member, John Patrick Vanden Heuvel, Committee Member, Avery August, Committee Member, Shantu G Amin, Committee Member.

Subjects/Keywords: selenium; Cyclooxygenase; Prostaglandin; IKKbeta; PG synthases; Oxidative stress

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Vunta, H. L. (2008). Redox regulation of the NF-kappaB pathway in macrophages: Role of 15-Deoxy-delta 12,14-prostaglandin J2. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/8266

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Vunta, Hema Latha. “Redox regulation of the NF-kappaB pathway in macrophages: Role of 15-Deoxy-delta 12,14-prostaglandin J2.” 2008. Thesis, Penn State University. Accessed March 07, 2021. https://submit-etda.libraries.psu.edu/catalog/8266.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Vunta, Hema Latha. “Redox regulation of the NF-kappaB pathway in macrophages: Role of 15-Deoxy-delta 12,14-prostaglandin J2.” 2008. Web. 07 Mar 2021.

Vancouver:

Vunta HL. Redox regulation of the NF-kappaB pathway in macrophages: Role of 15-Deoxy-delta 12,14-prostaglandin J2. [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Mar 07]. Available from: https://submit-etda.libraries.psu.edu/catalog/8266.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Vunta HL. Redox regulation of the NF-kappaB pathway in macrophages: Role of 15-Deoxy-delta 12,14-prostaglandin J2. [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/8266

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

13. DeGrazia, Michael. Design, Synthesis and Evaluation of Fluorescent Small Molecule Probes of Biological Systems .

Degree: 2008, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/7977

► Fluorescent derivatives of biologically active molecules are essential tools for studying molecular interactions at the cellular level. Fluorescent tags and/or labels have been used to… (more)

▼ Fluorescent derivatives of biologically active molecules are essential tools for studying molecular interactions at the cellular level. Fluorescent tags and/or labels have been used to study protein-protein interactions, intracellular localization of biomolecules and organelles, and small molecule-protein interactions. We report here studies of fluorescent ligands of Peroxisome Proliferator Activated Receptors (PPARs), protein targets under intense investigation for the treatment of human metabolic disorders. Such fluorescent ligands have the potential to enable faster identification of novel therapeutics. To pursue this goal, we synthesized a variety of fluorescent small molecule PPAR ligands for high-throughput examination of potential endogenous and exogenous ligands that bind these proteins. We found that our fluorescein labeled PPAR ligands bound PPARγ and PPARα with high selectivity and were good candidates for fluorescence polarization assays. In addition, we also utilized Pennsylvania Green as a more hydrophobic analogue of fluorescein to generate cell-permeable versions of these PPAR probes to develop a novel method for studying PPAR ligand binding in living cells, which can be further extended to other related members of the nuclear hormone receptor family. To extend previously reported studies on 3β-cholesterylamine derivatives that function as non-natural cell surface receptors, we synthesized a series of Oregon Green labeled symmetrical dimers of 3β-cholesterylamine as potential precursors to membrane spanning artificial cell surface receptors. We examined these compounds using confocal microscopy, flow cytometry, and spectroscopy to identify the optimal structural requirements for insertion into membranes of living mammalian cells. Modeled after our best compound, we synthesized an asymmetrical 3β-cholesterylamine dimer bearing Oregon Green as an extracellular fluorescent label and biotin as an intracellular ligand of streptavidin expressed in the cytosol. Examination of this dimer using confocal microscopy showed low cellular association, which could be due to the non-protonatable amide bearing biotin. Further studies to generate synthetic analogues bearing protonatable groups on the intracellular motif could project biotin into the cytosol and recruit streptavidin to the inner-leaflet of the membrane. Through intracellular control of protein localization it is postulated that asymmetrical cholesterylamines of this type could be used to influence internal cell signaling and cellular uptake pathways. Artificial cell surface receptors that span cellular membranes could provide a new strategy for controlling therapeutically relevant intracellular pathways. Advisors/Committee Members: Blake Peterson, Committee Chair/Co-Chair, Ken S Feldman, Committee Member, Ayusman Sen, Committee Member, John Patrick Vanden Heuvel, Committee Member.

Subjects/Keywords: PPAR; Cholesterol; Oregon Green; Cell Surface Receptors; Membrane Spanning

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

DeGrazia, M. (2008). Design, Synthesis and Evaluation of Fluorescent Small Molecule Probes of Biological Systems . (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/7977

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

DeGrazia, Michael. “Design, Synthesis and Evaluation of Fluorescent Small Molecule Probes of Biological Systems .” 2008. Thesis, Penn State University. Accessed March 07, 2021. https://submit-etda.libraries.psu.edu/catalog/7977.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

DeGrazia, Michael. “Design, Synthesis and Evaluation of Fluorescent Small Molecule Probes of Biological Systems .” 2008. Web. 07 Mar 2021.

Vancouver:

DeGrazia M. Design, Synthesis and Evaluation of Fluorescent Small Molecule Probes of Biological Systems . [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Mar 07]. Available from: https://submit-etda.libraries.psu.edu/catalog/7977.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

DeGrazia M. Design, Synthesis and Evaluation of Fluorescent Small Molecule Probes of Biological Systems . [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/7977

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

14. Gebauer, Sarah K. A COMPREHENSIVE DOSE-RESPONSE STUDY OF THE EFFECTS OF PISTACHIOS ON CARDIOVASCULAR DISEASE RISK FACTORS: A TRANSLATIONAL RESEARCH APPROACH INTEGRATING CLINICAL NUTRITION AND MOLECULAR BIOLOGY .

Degree: 2008, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/8225

► Nut consumption reduces risk for cardiovascular disease (CVD). Few studies have evaluated the effects of pistachios on CVD risk factors and they have not evaluated… (more)

▼ Nut consumption reduces risk for cardiovascular disease (CVD). Few studies have evaluated the effects of pistachios on CVD risk factors and they have not evaluated dose-response relationships or lipid-lowering mechanisms. Nutrition studies with a translational research approach integrate clinical nutrition and molecular biology, allowing for the investigation of clinical responses and underlying cellular mechanisms. The present study utilized a translational research approach to comprehensively evaluate the effects of pistachios on CVD. We employed a randomized crossover controlled-feeding study to evaluate the effects of two doses of pistachios, added to a lower-fat diet, on lipids and lipoproteins, apolipoprotein-defined lipoprotein subclasses, and plasma fatty acids. To investigate mechanisms of action, we measured serum cholesteryl ester transfer protein (CETP), indices of plasma stearoyl-CoA desaturase activity (SCD), and gene expression in isolated peripheral blood mononuclear cells (PBMCs). Total cholesterol (TC), LDL-C, non-HDL-C, apoB, and apoB/apoA-I decreased after both pistachio diets; and triacylglycerol and plasma SCD activity decreased after the 3.0 ounce pistachio diet (P < 0.05). Pistachios elicited a dose-dependent lowering of TC/HDL-C, LDL-C/HDL-C, and non-HDL-C/HDL-C (P < 0.01). We evaluated the effects of pistachios on expression of genes related to inflammation and lipid metabolism (TNFá, IL-1â, IL-6, ICAM, VCAM, CETP, and LCAT) in PBMCs. Furthermore, we investigated the relationship between diet-induced change in CETP expression and change in serum CETP and plasma lipids/lipoproteins. The pistachio-rich diets significantly decreased IL-1â expression compared to baseline (P < 0.05). Change in CETP expression in PBMCs predicted change in LDL-C, NONHDL-C, TC/HDL-C, and NONHDL-C/HDL-C in individuals who were diet-responsive with regards to serum CETP. In conclusion, this study demonstrates that pistachios elicit beneficial effects on traditional and emerging CVD risk factors at the protein level in serum/plasma and the transcription level in PBMCs. Advisors/Committee Members: Penny Margaret Kris Etherton, Committee Chair/Co-Chair, John Patrick Vanden Heuvel, Committee Member, Sheila Grace West, Committee Member, David Theodore Mauger, Committee Member.

Subjects/Keywords: peripheral blood mononuclear cells; cholesteryl ester transfer protein; cardiovascular disease risk; pistachios; lipids and lipoproteins; translational research

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Gebauer, S. K. (2008). A COMPREHENSIVE DOSE-RESPONSE STUDY OF THE EFFECTS OF PISTACHIOS ON CARDIOVASCULAR DISEASE RISK FACTORS: A TRANSLATIONAL RESEARCH APPROACH INTEGRATING CLINICAL NUTRITION AND MOLECULAR BIOLOGY . (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/8225

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Gebauer, Sarah K. “A COMPREHENSIVE DOSE-RESPONSE STUDY OF THE EFFECTS OF PISTACHIOS ON CARDIOVASCULAR DISEASE RISK FACTORS: A TRANSLATIONAL RESEARCH APPROACH INTEGRATING CLINICAL NUTRITION AND MOLECULAR BIOLOGY .” 2008. Thesis, Penn State University. Accessed March 07, 2021. https://submit-etda.libraries.psu.edu/catalog/8225.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Gebauer, Sarah K. “A COMPREHENSIVE DOSE-RESPONSE STUDY OF THE EFFECTS OF PISTACHIOS ON CARDIOVASCULAR DISEASE RISK FACTORS: A TRANSLATIONAL RESEARCH APPROACH INTEGRATING CLINICAL NUTRITION AND MOLECULAR BIOLOGY .” 2008. Web. 07 Mar 2021.

Vancouver:

Gebauer SK. A COMPREHENSIVE DOSE-RESPONSE STUDY OF THE EFFECTS OF PISTACHIOS ON CARDIOVASCULAR DISEASE RISK FACTORS: A TRANSLATIONAL RESEARCH APPROACH INTEGRATING CLINICAL NUTRITION AND MOLECULAR BIOLOGY . [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Mar 07]. Available from: https://submit-etda.libraries.psu.edu/catalog/8225.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Gebauer SK. A COMPREHENSIVE DOSE-RESPONSE STUDY OF THE EFFECTS OF PISTACHIOS ON CARDIOVASCULAR DISEASE RISK FACTORS: A TRANSLATIONAL RESEARCH APPROACH INTEGRATING CLINICAL NUTRITION AND MOLECULAR BIOLOGY . [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/8225

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

15. Foreman, Jennifer E. PRENATAL NICOTINE EXPOSURE ALTERS GENE EXPRESSION IN A SEXUALLY DIMORPHIC MANNER.

Degree: 2008, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/7627

► Nicotine has been demonstrated to regulate gene expression in brain reward pathways. In human adults these changes in expression are hypothesized to play a role… (more)

Subjects/Keywords: prenatal nicotine; microarray; Pou3f1; Kif1a; gene networks; sex differences

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Foreman, J. E. (2008). PRENATAL NICOTINE EXPOSURE ALTERS GENE EXPRESSION IN A SEXUALLY DIMORPHIC MANNER. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/7627

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Foreman, Jennifer E. “PRENATAL NICOTINE EXPOSURE ALTERS GENE EXPRESSION IN A SEXUALLY DIMORPHIC MANNER.” 2008. Thesis, Penn State University. Accessed March 07, 2021. https://submit-etda.libraries.psu.edu/catalog/7627.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Foreman, Jennifer E. “PRENATAL NICOTINE EXPOSURE ALTERS GENE EXPRESSION IN A SEXUALLY DIMORPHIC MANNER.” 2008. Web. 07 Mar 2021.

Vancouver:

Foreman JE. PRENATAL NICOTINE EXPOSURE ALTERS GENE EXPRESSION IN A SEXUALLY DIMORPHIC MANNER. [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Mar 07]. Available from: https://submit-etda.libraries.psu.edu/catalog/7627.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Foreman JE. PRENATAL NICOTINE EXPOSURE ALTERS GENE EXPRESSION IN A SEXUALLY DIMORPHIC MANNER. [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/7627

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

16. De Keyser, Joshua Gordon. ALTERNATIVE SPLICING OF THE HUMAN CONSTITUTIVE ANDROSTANE RECEPTOR GENE CREATES RECEPTORS WITH UNIQUE FUNCTION AND LIGAND SPECIFICITY .

Degree: 2009, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/9350

► The human constitutive androstane receptor (CAR) regulates the expression of genes involved in xenobiotic metabolism in the liver. The CAR gene utilizes multiple alternative splicing… (more)

▼ The human constitutive androstane receptor (CAR) regulates the expression of genes involved in xenobiotic metabolism in the liver. The CAR gene utilizes multiple alternative splicing events during pre-mRNA processing, thereby increasing the CAR transcriptome. The work presented in this dissertation focuses on the functional analysis of a prominent human CAR variant, CAR2 that possesses a 4- amino acid insertion in the ligand binding domain. Previous investigations led us to hypothesize that the CAR2 variant is a ligand-activated receptor and possesses a unique ligand binding profile giving rise to novel biological function. We now demonstrate that CAR2 constitutes approximately one-third and one-half of the total CAR transcriptome in human hepatocytes and small intestine, respectively. Further, we identify the common plasticizers, di(2-ethylhexyl) phthalate (DEHP) and di-isononyl phthalate (DiNP) as highly potent and uniquely selective agonists of CAR2. Results from reporter transactivation assays reveal that DEHP and DiNP activate CAR2 at low nanomolar concentrations. In addition, comparative genomic analysis show that the typical mouse, rat and marmoset models of toxicity can not accurately profile potential human toxicity due to these species inability to generate a CAR2-like transcript. It is also demonstrated that CAR2 possesses an altered ligand pocket that allows for the highly potent and specific activation of the variant by DEHP and DiNP. Further studies show that CAR1 and CAR3 share similar ligand activation profiles; whereas CAR2 responds to most CAR1 and CAR3 ligands as well as a unique subset of chemicals. Finally, it is now shown that meclizine, a human CAR1 inverse-agonist, is a specific agonist of CAR2. A meclizine derived pharmacophore was utilized in a ligand-based virtual screening and identified two novel CAR2 agonists from the NCI chemical database. The results of this dissertation will aid in the development of better models of human CAR activation, give a more complete understanding of the interaction of CAR with xenobiotics, yield novel insight into potential mechanisms of phthalate toxicity and provide the foundation for future studies into the physiologic functions of alternatively spliced variants of CAR. Advisors/Committee Members: Curtis John Omiecinski, Dissertation Advisor/Co-Advisor, Curtis John Omiecinski, Committee Chair/Co-Chair, Reka Z Albert, Committee Member, Adam Bleier Glick, Committee Member, John Patrick Vanden Heuvel, Committee Member.

Subjects/Keywords: phthalates; alternative splicing; constitutive androstane receptor; drug and xenobiotic metabolism; meclizine; nuclear receptors; gene induction

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

De Keyser, J. G. (2009). ALTERNATIVE SPLICING OF THE HUMAN CONSTITUTIVE ANDROSTANE RECEPTOR GENE CREATES RECEPTORS WITH UNIQUE FUNCTION AND LIGAND SPECIFICITY . (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/9350

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

De Keyser, Joshua Gordon. “ALTERNATIVE SPLICING OF THE HUMAN CONSTITUTIVE ANDROSTANE RECEPTOR GENE CREATES RECEPTORS WITH UNIQUE FUNCTION AND LIGAND SPECIFICITY .” 2009. Thesis, Penn State University. Accessed March 07, 2021. https://submit-etda.libraries.psu.edu/catalog/9350.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

De Keyser, Joshua Gordon. “ALTERNATIVE SPLICING OF THE HUMAN CONSTITUTIVE ANDROSTANE RECEPTOR GENE CREATES RECEPTORS WITH UNIQUE FUNCTION AND LIGAND SPECIFICITY .” 2009. Web. 07 Mar 2021.

Vancouver:

De Keyser JG. ALTERNATIVE SPLICING OF THE HUMAN CONSTITUTIVE ANDROSTANE RECEPTOR GENE CREATES RECEPTORS WITH UNIQUE FUNCTION AND LIGAND SPECIFICITY . [Internet] [Thesis]. Penn State University; 2009. [cited 2021 Mar 07]. Available from: https://submit-etda.libraries.psu.edu/catalog/9350.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

De Keyser JG. ALTERNATIVE SPLICING OF THE HUMAN CONSTITUTIVE ANDROSTANE RECEPTOR GENE CREATES RECEPTORS WITH UNIQUE FUNCTION AND LIGAND SPECIFICITY . [Thesis]. Penn State University; 2009. Available from: https://submit-etda.libraries.psu.edu/catalog/9350

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

17. Zamule, Stephanie M. ROLE OF THE CONSTITUTIVE ANDROSTANE RECEPTOR IN THE DERIVATION OF HEPATIC-LIKE CELLS FROM HUMAN EMBRYONIC STEM CELLS.

Degree: 2010, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/10496

► The liver performs an array of functions vital to life including detoxification, production of serum proteins, maintenance of cholesterol homeostasis, production and clearance of bile… (more)

▼ The liver performs an array of functions vital to life including detoxification, production of serum proteins, maintenance of cholesterol homeostasis, production and clearance of bile components, assembly and inter-conversion of amino acids, synthesis and breakdown of glucose, and processing of fatty acids. Current treatments for liver failure are inadequate, relying on liver or hepatocyte transplantation, both of which are significantly limited by insufficient donor tissue, donor-to-donor variability in tissue quality, and the risk of rejection, infection, or adverse immune response in the recipient. Human embryonic stem cells (hESCs) – derived from the inner cell mass of developing blastocysts and capable of giving rise to any cell type in the body upon exposure to the appropriate conditions – offer promise as an alternative source of cells from which a supply of hepatocytes may be derived for therapeutic transplantations. Hepatocytes derived from hESCs would also potentially provide a repository of cells for pharmacological and toxicological studies which rely on hepatocytes obtained from human donors as models for drug metabolism research and predictors of toxicological responses that may be associated with exposure to xenobiotic compounds. While a number of studies have demonstrated that hESCs are capable of differentiating into hepatic precursors, the precise means by which these cells may be derived, and the genes governing this multifaceted process, have yet to be fully elucidated. In this investigation we employed a unique hepatic differentiation protocol in which hESCs are cultured for only 10 days on collagen matrix in our hepatocyte media (William’s E Media supplemented with HEPES, glutamine, antibiotics, dexamethasone, insulin, transferrin, selenium, and linoleic acid/albumin). The resulting cell population exhibits hepatic-like cell morphology and decreased expression of ‘stemness’ markers including certain transcription factors, surface antigens, and enzymes. The hESC-derived hepatic-like cells express enhanced levels of hepatic markers including transcription factors, nuclear receptors, liver-generated plasma proteins, protease inhibitors, metabolic enzymes, and biotransformation enzymes. Acquisition of hepatic function is confirmed by the cells’ ability to transport anionic compounds and store glycogen. Notably, expression of the constitutive androstane receptor (CAR) – a nuclear receptor which, in the adult liver, is involved in the regulation of diverse physiological processes including all three phases of hepatic biotransformation and elimination as well as energy metabolism and lipid homeostasis – is highly increased in the hepatic-like cells, to levels approaching those of cultures of primary human hepatocytes. CAR is also expressed robustly and consistently in human fetal liver tissue obtained from subjects of a range of gestational ages. Modulation of CAR levels in differentiating hESCs using a lentivirus system – which we demonstrate to stably and robustly transduce both hESCs and cultures… Advisors/Committee Members: Curtis John Omiecinski, Dissertation Advisor/Co-Advisor, Curtis John Omiecinski, Committee Chair/Co-Chair, Gong Chen, Committee Member, Peter John Hudson, Committee Member, Gary H Perdew, Committee Member, John Patrick Vanden Heuvel, Committee Member, Kent Eugene Vrana, Committee Member.

Subjects/Keywords: embryonic stem cells; constitutive androstane receptor; liver; differentiation; nuclear receptor; development; lentivirus

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Zamule, S. M. (2010). ROLE OF THE CONSTITUTIVE ANDROSTANE RECEPTOR IN THE DERIVATION OF HEPATIC-LIKE CELLS FROM HUMAN EMBRYONIC STEM CELLS. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/10496

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Zamule, Stephanie M. “ROLE OF THE CONSTITUTIVE ANDROSTANE RECEPTOR IN THE DERIVATION OF HEPATIC-LIKE CELLS FROM HUMAN EMBRYONIC STEM CELLS.” 2010. Thesis, Penn State University. Accessed March 07, 2021. https://submit-etda.libraries.psu.edu/catalog/10496.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Zamule, Stephanie M. “ROLE OF THE CONSTITUTIVE ANDROSTANE RECEPTOR IN THE DERIVATION OF HEPATIC-LIKE CELLS FROM HUMAN EMBRYONIC STEM CELLS.” 2010. Web. 07 Mar 2021.

Vancouver:

Zamule SM. ROLE OF THE CONSTITUTIVE ANDROSTANE RECEPTOR IN THE DERIVATION OF HEPATIC-LIKE CELLS FROM HUMAN EMBRYONIC STEM CELLS. [Internet] [Thesis]. Penn State University; 2010. [cited 2021 Mar 07]. Available from: https://submit-etda.libraries.psu.edu/catalog/10496.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Zamule SM. ROLE OF THE CONSTITUTIVE ANDROSTANE RECEPTOR IN THE DERIVATION OF HEPATIC-LIKE CELLS FROM HUMAN EMBRYONIC STEM CELLS. [Thesis]. Penn State University; 2010. Available from: https://submit-etda.libraries.psu.edu/catalog/10496

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

18. Wei, Xin. REGULATION OF RECEPTOR ACTIVITY AND SPECIFICITY: LESSONS LEARNED FROM THE EVOLUTIONARY DIVERGENCE OF HUMAN AND MOUSE RON RECEPTOR TYROSINE KINASES .

Degree: 2008, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/6714

► Deregulation of receptor tyrosine kinases is implicated in a wide range of human diseases including tumorigenesis and autoimmunity. Oncogenic mutations of RTKs can also serve… (more)

▼ Deregulation of receptor tyrosine kinases is implicated in a wide range of human diseases including tumorigenesis and autoimmunity. Oncogenic mutations of RTKs can also serve as powerful experimental models for understanding the mechanisms of receptor regulation. In this current study, we demonstrate that, in contrast with human Ron (hRon), murine Ron (mRon) displays strong receptor activity and downstream signaling capacity, despite the high degree of sequence conservation between these two orthologous receptors. The main goal of this work is to study the activity and signaling specificity of the receptor by mapping the evolutionary divergence of these two homologous proteins that is responsible for their functional differences. Alternative splicing of signaling proteins can contribute to the complexity of signaling networks. Splicing of the mouse Ron transcript results in the constitutive deletion of an exon used by all other known Ron orthologs, which encodes part of the juxtamembrane (JM) region of the receptor. This partial deletion in the juxtamembrane domain of mouse Ron results in enhanced receptor autophosphorylation and ligand-independent activation of the Ras-p42/44 MAP kinase pathway. In contrast to the ligand-dependent recruitment of a Grb2-Sos complex that requires the autophosphorylation of C-terminal tyrosines, ligand-independent MAP activation is c-Src-dependent and independent of Grb2 and the docking site tyrosines. Furthermore, we show that the mouse Ron juxtamembrane domain controls the association of c-Src with the receptor in a SH2 dependent manner. These data provide direct evidence that the divergence of exon usage among different species can generate a protein with novel activity and subsequently add to the complexity of cellular signaling regulation. Progressive deletions of the mRon C-terminal tail reveal that the constitutive activation of the Erk-Fos pathway is independent of the entire carboxyl tail of the receptor, requiring only the integrity of tyrosine kinase domain. Among the 12 tyrosines in the intracellular region of Ron, we identified three tyrosines (Tyr1175, Tyr1265, Tyr1294) within the kinase domain that play critical but overlapping roles in controlling constitutive Erk activation by mRon. mRon harboring tyrosine to phenylalanine mutations at these three sites loses the capability to constitutively activate the Erk-Fos pathway. However, this mutant retains the ability to activate this pathway in response to ligand stimulation. Thus, the ligand dependent and constitutive activity of the mRon receptor can be uncoupled through the alteration of selective sets of tyrosines. Finally, the restoration of one of these three tyrosines results in the recruitment of c-Src by the receptor, highlighting the possibility that those tyrosines might serve as potential c-Src SH2 domain binding site in the absence of ligand. The chimeric studies indicate that, in addition to the JM domain, differences in the kinase domain of hRon and mRon also… Advisors/Committee Members: Pamela Hankey Giblin, Committee Chair/Co-Chair, Andrew Thomas Henderson, Committee Member, Avery August, Committee Member, Robert Paulson, Committee Member, John Patrick Vanden Heuvel, Committee Member, Jia Li, Committee Member.

Subjects/Keywords: Erk; signaling; receptor tyrosine kinase; Ron; Src; Juxtamembrane domain

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Wei, X. (2008). REGULATION OF RECEPTOR ACTIVITY AND SPECIFICITY: LESSONS LEARNED FROM THE EVOLUTIONARY DIVERGENCE OF HUMAN AND MOUSE RON RECEPTOR TYROSINE KINASES . (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/6714

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Wei, Xin. “REGULATION OF RECEPTOR ACTIVITY AND SPECIFICITY: LESSONS LEARNED FROM THE EVOLUTIONARY DIVERGENCE OF HUMAN AND MOUSE RON RECEPTOR TYROSINE KINASES .” 2008. Thesis, Penn State University. Accessed March 07, 2021. https://submit-etda.libraries.psu.edu/catalog/6714.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Wei, Xin. “REGULATION OF RECEPTOR ACTIVITY AND SPECIFICITY: LESSONS LEARNED FROM THE EVOLUTIONARY DIVERGENCE OF HUMAN AND MOUSE RON RECEPTOR TYROSINE KINASES .” 2008. Web. 07 Mar 2021.

Vancouver:

Wei X. REGULATION OF RECEPTOR ACTIVITY AND SPECIFICITY: LESSONS LEARNED FROM THE EVOLUTIONARY DIVERGENCE OF HUMAN AND MOUSE RON RECEPTOR TYROSINE KINASES . [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Mar 07]. Available from: https://submit-etda.libraries.psu.edu/catalog/6714.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Wei X. REGULATION OF RECEPTOR ACTIVITY AND SPECIFICITY: LESSONS LEARNED FROM THE EVOLUTIONARY DIVERGENCE OF HUMAN AND MOUSE RON RECEPTOR TYROSINE KINASES . [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/6714

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

19. Markell, Lauren Mordasky. PHARMACOLOGICAL INHIBITION OF THE TGF-BETA TYPE I RECEPTOR REVEALS A DUAL ROLE OF TGF-BETA IN CARCINOGENESIS .

Degree: 2010, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/11358

► Transforming growth factor-beta 1 (TGF-beta 1) is a member of a large family of regulatory molecules that play both positive and negative roles in epithelial… (more)

▼ Transforming growth factor-beta 1 (TGF-beta 1) is a member of a large family of regulatory molecules that play both positive and negative roles in epithelial cancer. Pharmacological inhibitors of the Transforming Growth Factor-beta (TGF-beta) type I receptor (ALK5) have shown promise in blocking growth of xenotransplanted cancer cell lines but the effect on a multistage cancer model is not known. In the present studies, the role of the ALK5 inhibitor SB431542 (SB) was investigated in a two-stage skin chemical carcinogenesis assay in order to determine the effect on tumor formation and progression. In this model, nearly all tumors have activating mutations in codon 61 of the HRas gene. We show that topical SB significantly reduced the total number, incidence and size of papillomas compared to 12-O-tetradecanoylphorbol 13-acetate (TPA) promotion alone, and this was linked to increased epidermal apoptosis, decreased proliferation and decreased cutaneous inflammation during promotion. In contrast, the frequency of conversion to squamous cell carcinoma (SCC) was two-fold higher in papillomas treated with SB. While there was no difference in tumor cell proliferation in early premalignant lesions, those that formed after SB treatment exhibited reduced squamous differentiation and an altered inflammatory microenvironment similar to SCC. In an inducible epidermal HRAS transgenic model, treatment with SB enhanced proliferation and cutaneous inflammation in skin, but decreased expression of keratin 1 and increased expression of simple epithelial keratin 18, markers of premalignant progression. In agreement with increased frequency of progression in the multistage model, SB treatment resulted in increased tumor formation with a more malignant phenotype following long-term HRAS induction. To further characterize the altered squamous differentiation associated with reduced tumor formation and increased malignant progression by ALK5 inhibition, an HRAS oncogene-induced model of preneoplastic keratinocytes was utilized. SB significantly enhanced HRAS-induced cornification which correlated with the increased expression of terminal differentiation genes transglutaminase 1 (TGM1) and 3 (TGM3) and small proline-rich protein 1A (SPR1A) and 2H (SPR2H) which cross-link structural proteins that make up the cornified envelope. There was a similar increase in cornified layers and TGM and SPR gene expression following SB treatment of mice expressing inducible epidermal HRAS. Alternatively, treatment of HRAS-expressing keratinocytes with TGF-beta 1 or overexpression of TGF-beta 1 and HRAS in an inducible epidermal transgenic model resulted in reduced expression of TGM1 and TGM3 and cornification in vitro. Papilloma (SP1) and squamous cell carcinoma (PAM2.12) cell lines were less responsive to TGF-beta 1 suppression of markers and marker induction by SB. Interestingly, a subpopulation of HRAS-expressing keratinocytes were resistant to induction of terminal differentiation by ALK5 inhibition. These cells were also resistant to senescence and… Advisors/Committee Members: Adam Bleier Glick, Dissertation Advisor/Co-Advisor, Adam Bleier Glick, Committee Chair/Co-Chair, John Patrick Vanden Heuvel, Committee Member, Gary H Perdew, Committee Member, Zhi Chun Lai, Committee Member, Jeffrey Maurice Peters, Committee Member.

Subjects/Keywords: skin; skin carcinogenesis; TGF-beta; chemically-induced carcinogenesis

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Markell, L. M. (2010). PHARMACOLOGICAL INHIBITION OF THE TGF-BETA TYPE I RECEPTOR REVEALS A DUAL ROLE OF TGF-BETA IN CARCINOGENESIS . (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/11358

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Markell, Lauren Mordasky. “PHARMACOLOGICAL INHIBITION OF THE TGF-BETA TYPE I RECEPTOR REVEALS A DUAL ROLE OF TGF-BETA IN CARCINOGENESIS .” 2010. Thesis, Penn State University. Accessed March 07, 2021. https://submit-etda.libraries.psu.edu/catalog/11358.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Markell, Lauren Mordasky. “PHARMACOLOGICAL INHIBITION OF THE TGF-BETA TYPE I RECEPTOR REVEALS A DUAL ROLE OF TGF-BETA IN CARCINOGENESIS .” 2010. Web. 07 Mar 2021.

Vancouver:

Markell LM. PHARMACOLOGICAL INHIBITION OF THE TGF-BETA TYPE I RECEPTOR REVEALS A DUAL ROLE OF TGF-BETA IN CARCINOGENESIS . [Internet] [Thesis]. Penn State University; 2010. [cited 2021 Mar 07]. Available from: https://submit-etda.libraries.psu.edu/catalog/11358.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Markell LM. PHARMACOLOGICAL INHIBITION OF THE TGF-BETA TYPE I RECEPTOR REVEALS A DUAL ROLE OF TGF-BETA IN CARCINOGENESIS . [Thesis]. Penn State University; 2010. Available from: https://submit-etda.libraries.psu.edu/catalog/11358

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

20. Smith, Terry Michael. THE INVOLVEMENT OF THE STEROL RESPONSE ELEMENT BINDING PROTEINS IN LIPOGENESIS IN THE SEB-1 SEBACEOUS MODEL SYSTEM .

Degree: 2008, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/7390

► Excessive lipid production is an integral factor in the pathogenesis of acne. As such, an understanding of the molecular signaling involved in sebaceous gland lipid… (more)

▼ Excessive lipid production is an integral factor in the pathogenesis of acne. As such, an understanding of the molecular signaling involved in sebaceous gland lipid production is needed to identify therapeutic targets to improve acne. The sterol response element binding proteins (SREBPs) are a class of transcription factors known to regulate lipid production, particularly in response to insulin in the liver. We hypothesize that the SREBPs are important in sebaceous gland lipid metabolism, and thus represent a potential drug target for the treatment of acne. The correlation between severity of acne and insulin-like growth factor-1 (IGF-1) levels in women led us to investigate the effects of IGF-1 on sebaceous lipid production and SREBP-1 levels. The work described in this thesis demonstrates that IGF-1 increases both lipogenesis and SREBP protein levels in SEB-1 sebocytes. Furthermore, a variety of growth factors have been shown to increase SREBP mRNA and protein in many different model systems. However, the signaling pathway(s) that are important to transducing the growth factor signal seems to vary by cell type. We have found that IGF-1 stimulation activates both the PI3-K and the MAPK/ERK pathways in SEB-1 cells. As both of these pathways have been found to be responsible for growth factor stimulated increases of SREBP, we sought to determine if one or both pathways were important for the IGF-1 induced lipogenesis and increase in SREBP that we have observed in the SEB-1 cells. We report that treatment with the PI3-K inhibitor LY294002 completely blocks IGF-1 induced lipogenesis and SREBP transcription, translation, and processing in SEB-1 cells whereas the MAPK/ERK pathway inhibitor PD98059 has no effect on lipogenesis or SREBP protein induction. These data indicate the PI3-K is the primary signaling pathway involved in lipogenesis in SEB-1 sebocytes. In summary, this work provides evidence that SREBP-1 is a potential drug target for the reduction of lipid production in the treatment of acne. Furthermore, these data provide a rationale for the investigation of specific inhibitors to the individual members of the PI3-K family for treatment of acne. Advisors/Committee Members: Gary Alan Clawson, Committee Chair/Co-Chair, Diane M Thiboutot, Committee Chair/Co-Chair, Melvin Lee Billingsley, Committee Member, Craig Matthew Meyers, Committee Member, John Patrick Vanden Heuvel, Committee Member.

Subjects/Keywords: sterol response element binding protein; SREBP; lipogenesis; acne; sebaceous gland; IGF-1; insulin-like growth factor

Record Details Similar Records Cite « Share

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Smith, T. M. (2008). THE INVOLVEMENT OF THE STEROL RESPONSE ELEMENT BINDING PROTEINS IN LIPOGENESIS IN THE SEB-1 SEBACEOUS MODEL SYSTEM . (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/7390

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Smith, Terry Michael. “THE INVOLVEMENT OF THE STEROL RESPONSE ELEMENT BINDING PROTEINS IN LIPOGENESIS IN THE SEB-1 SEBACEOUS MODEL SYSTEM .” 2008. Thesis, Penn State University. Accessed March 07, 2021. https://submit-etda.libraries.psu.edu/catalog/7390.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Smith, Terry Michael. “THE INVOLVEMENT OF THE STEROL RESPONSE ELEMENT BINDING PROTEINS IN LIPOGENESIS IN THE SEB-1 SEBACEOUS MODEL SYSTEM .” 2008. Web. 07 Mar 2021.

Vancouver:

Smith TM. THE INVOLVEMENT OF THE STEROL RESPONSE ELEMENT BINDING PROTEINS IN LIPOGENESIS IN THE SEB-1 SEBACEOUS MODEL SYSTEM . [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Mar 07]. Available from: https://submit-etda.libraries.psu.edu/catalog/7390.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Smith TM. THE INVOLVEMENT OF THE STEROL RESPONSE ELEMENT BINDING PROTEINS IN LIPOGENESIS IN THE SEB-1 SEBACEOUS MODEL SYSTEM . [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/7390

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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Open Access Theses and Dissertations