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You searched for +publisher:"University of Texas Southwestern Medical Center" +contributor:("Hofmann, Sandra L."). Showing records 1 – 2 of 2 total matches.

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University of Texas Southwestern Medical Center

1. Chakrabarti, Rima Shah. Variability of Cholesterol Accessibility in Human Red Blood Cells Measured Using a Bacterial Cholesterol Binding Toxin.

Degree: 2017, University of Texas Southwestern Medical Center

Cholesterol partitions into accessible and sequestered pools in cell membranes. Here, we describe a new assay using fluorescently-tagged anthrolysin O, a cholesterol-binding bacterial toxin, to measure accessible cholesterol in human red blood cells (RBCs). Accessible cholesterol levels were stable within individuals, but varied >10 fold among individuals. Significant variation was observed among ethnic groups (Blacks>Hispanics>Whites). Variation in accessibility of RBC cholesterol was unrelated to the cholesterol content of RBCs or plasma, but was associated with the phospholipid composition of the RBC membranes and with plasma triglyceride levels. Pronase treatment of RBCs only modestly altered cholesterol accessibility. Plasma from various healthy individuals differentially modulated RBC cholesterol accessibility. Individuals on hemodialysis, who have an unexplained increase in atherosclerotic risk, had significantly higher RBC cholesterol accessibility. Our data indicate that RBC accessible cholesterol is a stable phenotype with significant inter-individual variability. Factors both intrinsic and extrinsic to the RBC contribute to variation in its accessibility. This assay provides a new tool to assess cholesterol homeostasis among tissues in humans. Advisors/Committee Members: Radhakrishnan, Arun, Horton, Jay D., Hofmann, Sandra L..

Subjects/Keywords: Bacterial Proteins; Cholesterol; Erythrocytes; Membrane Glycoproteins

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

APA (6th Edition):

Chakrabarti, R. S. (2017). Variability of Cholesterol Accessibility in Human Red Blood Cells Measured Using a Bacterial Cholesterol Binding Toxin. (Thesis). University of Texas Southwestern Medical Center. Retrieved from http://hdl.handle.net/2152.5/6605

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

Chicago Manual of Style (16th Edition):

Chakrabarti, Rima Shah. “Variability of Cholesterol Accessibility in Human Red Blood Cells Measured Using a Bacterial Cholesterol Binding Toxin.” 2017. Thesis, University of Texas Southwestern Medical Center. Accessed March 30, 2020. http://hdl.handle.net/2152.5/6605.

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

MLA Handbook (7th Edition):

Chakrabarti, Rima Shah. “Variability of Cholesterol Accessibility in Human Red Blood Cells Measured Using a Bacterial Cholesterol Binding Toxin.” 2017. Web. 30 Mar 2020.

Vancouver:

Chakrabarti RS. Variability of Cholesterol Accessibility in Human Red Blood Cells Measured Using a Bacterial Cholesterol Binding Toxin. [Internet] [Thesis]. University of Texas Southwestern Medical Center; 2017. [cited 2020 Mar 30]. Available from: http://hdl.handle.net/2152.5/6605.

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

Council of Science Editors:

Chakrabarti RS. Variability of Cholesterol Accessibility in Human Red Blood Cells Measured Using a Bacterial Cholesterol Binding Toxin. [Thesis]. University of Texas Southwestern Medical Center; 2017. Available from: http://hdl.handle.net/2152.5/6605

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


University of Texas Southwestern Medical Center

2. Wang, Michael Leechun. The Hydrophobic Handoff Between NPC2 and the N-Terminal Domain of NPC1 in the Export of Cholesterol from Lysosomes.

Degree: 2013, University of Texas Southwestern Medical Center

Low density lipoproteins (LDL) and related plasma lipoproteins deliver cholesterol to cells by receptor-mediated endocytosis. The lipoprotein is degraded in late endosomes and lysosomes where its cholesterol is released. Egress of cholesterol from late endosomes and lysosomes (hereafter referred to as lysosomes) requires two proteins: Niemann-Pick C2 (NPC2), a soluble protein of 132 amino acids; and NPC1, an intrinsic membrane protein of 1278 amino acids and 13 postulated membrane-spanning helices that span the lysosomal membrane. Recessive loss-of-function mutations in either NPC2 or NPC1 produce NPC disease, which causes death in childhood owing to cholesterol accumulation in lysosomes of liver, brain, and lung. Consistent with their cholesterol export role, NPC2 and NPC1 both bind cholesterol. The cholesterol binding site on NPC1 is located in the NH2-terminal domain (NTD), which projects into the lysosomal lumen. This domain, designated NPC1(NTD), can be expressed in vitro as a soluble protein of 240 amino acids that retains cholesterol binding activity. This thesis studies NPC2 and NPC1(NTD) in detail as summarized below. Two major differences exist between the cholesterol binding of NPC2 and NPC1(NTD). 1) Competitive binding studies and crystal structures indicate that the two proteins bind cholesterol in opposite orientations. NPC2 binds the iso-octyl side chain, leaving the 3ß hydroxyl exposed, whereas NPC1 binds the 3ß-hydroxyl, leaving the side chain partially exposed. 2) Kinetic studies of cholesterol binding reveal that NPC2 binds and releases cholesterol rapidly (half-time < 2 min at 4 °C), while NPC1(NTD) binds cholesterol very slowly (half-time > 2 hr at 4 °C). Its rapid cholesterol binding allows NPC2 to transfer cholesterol to and from liposomes. Unlike NPC2, NPC1(NTD) cannot rapidly transfer its bound cholesterol to liposomes. However, NPC1(NTD) can accomplish this delivery when NPC2 is present. Furthermore, cholesterol binding to NPC1(NTD) is accelerated by >15-fold when the sterol is first bound to NPC2 and then transferred to NPC1(NTD). These data led us to advance a model in which NPC2 can mediate bi-directional transfer of cholesterol to or from NPC1(NTD). In cells, we envision that NPC2 accepts cholesterol in the lysosomal lumen and transports it to membrane-bound NPC1, thus accounting for the requirement for both proteins for lysosomal cholesterol export. Amino acid residues important or binding or transfer of cholesterol on NPC2 and NPC1(NTD) were identified through alanine scan mutagenesis. For both NPC2 and NPC1(NTD), residues that decreased binding mapped to areas surrounding the binding pockets on the crystal structures; residues that decreased transfer, but not binding, mapped to discrete surface patches near the opening of the binding pockets. These surface patches may be sites where the two proteins interact to transfer cholesterol. The most severe mutations disrupting binding were P120S for NPC2 and P202A/F203A for NPC1(NTD); and those that disrupted transfer were V81D… Advisors/Committee Members: Brown, Michael S., Goldstein, Joseph L., Thomas, Philip J., Roth, Michael G., Hofmann, Sandra L., Liang, Guosheng.

Subjects/Keywords: Carrier Proteins; Cholesterol; Glycoproteins; Lysosomes

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

APA (6th Edition):

Wang, M. L. (2013). The Hydrophobic Handoff Between NPC2 and the N-Terminal Domain of NPC1 in the Export of Cholesterol from Lysosomes. (Thesis). University of Texas Southwestern Medical Center. Retrieved from http://hdl.handle.net/2152.5/1708

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

Chicago Manual of Style (16th Edition):

Wang, Michael Leechun. “The Hydrophobic Handoff Between NPC2 and the N-Terminal Domain of NPC1 in the Export of Cholesterol from Lysosomes.” 2013. Thesis, University of Texas Southwestern Medical Center. Accessed March 30, 2020. http://hdl.handle.net/2152.5/1708.

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

MLA Handbook (7th Edition):

Wang, Michael Leechun. “The Hydrophobic Handoff Between NPC2 and the N-Terminal Domain of NPC1 in the Export of Cholesterol from Lysosomes.” 2013. Web. 30 Mar 2020.

Vancouver:

Wang ML. The Hydrophobic Handoff Between NPC2 and the N-Terminal Domain of NPC1 in the Export of Cholesterol from Lysosomes. [Internet] [Thesis]. University of Texas Southwestern Medical Center; 2013. [cited 2020 Mar 30]. Available from: http://hdl.handle.net/2152.5/1708.

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

Council of Science Editors:

Wang ML. The Hydrophobic Handoff Between NPC2 and the N-Terminal Domain of NPC1 in the Export of Cholesterol from Lysosomes. [Thesis]. University of Texas Southwestern Medical Center; 2013. Available from: http://hdl.handle.net/2152.5/1708

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

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