Advanced search options

Advanced Search Options 🞨

Browse by author name (“Author name starts with…”).

Find ETDs with:

in
/  
in
/  
in
/  
in

Written in Published in Earliest date Latest date

Sorted by

Results per page:

You searched for +publisher:"Vanderbilt University" +contributor:("Dr. BethAnn McLaughlin"). One record found.

Search Limiters

Last 2 Years | English Only

No search limiters apply to these results.

▼ Search Limiters


Vanderbilt University

1. Stankowski, Jeannette Nicole. Role of C-terminus of HSC70 interacting protein in determining neuronal fate in acute injury.

Degree: PhD, Neuroscience, 2011, Vanderbilt University

ROLE OF C-TERMINUS OF HSC70 INTERACTING PROTEIN IN DETERMINING NEURONAL FATE IN ACUTE INJURY JEANNETTE N. STANKOWSKI Dissertation under the direction of Professor BethAnn McLaughlin The decision to remove or refold oxidized, denatured or misfolded proteins by heat shock protein 70 (HSP70) and its binding partners is critical to determine cell fate. Acute overexpression of the ubiquitin ligase C-terminus of HSC70 interacting protein (CHIP) can compensate for failure of other ubiquitin ligases and enhance protein turnover and survival under chronic neurological stress. CHIP√Ęs ability to alter cell fate following acute neurological injury has however, not been assessed. Using post-mortem human tissue samples, we provide first evidence that cortical CHIP expression is increased following ischemic stroke. Oxygen glucose deprivation in vitro led to rapid protein oxidation, antioxidant depletion, proteasome dysfunction and a significant increase in CHIP. To determine if CHIP upregulation enhances neural survival, we overexpressed CHIP in vitro and evaluated cell fate 24hr following oxidative stress. Surprisingly, we observed that CHIP overexpressing cell lines fared worse against acute oxidative injury, accumulated more ubiquitinated and oxidized proteins and experienced decreased baseline proteasome activity suggesting that long-term upregulation of CHIP can be maladaptive. Conversely, decreasing CHIP expression in primary neuronal cultures using siRNA improved survival following oxidative stress, suggesting that the observed increase in CHIP following stroke-like injuries may negatively impact the neuroprotective potential of HSP70. To determine if cellular outcome could be further increased in an acute injury setting, we moved to a CHIP knockout model system and found increased levels of total oxidized proteins in brain tissue and accelerated calcium-induced mitochondrial permeability transition activities in these mice. Using the biotin-avidin-capture methodology to identify specific protein targets of oxidative stress, we found that known modulators of mitochondrial homeostasis or dynamics were not oxidatively modified. These results support previous findings of decreased lifespan and impaired survival upon injury observed in CHIP deficient animals. Together, these data suggest that CHIP expression must be tightly regulated in an acute injury setting as CHIP plays an essential role in regulating neuronal redox tone, and that strategies aimed at increasing CHIP expression levels may have previously unappreciated deleterious effects. Advisors/Committee Members: Dr. Pat Levitt (chair), Dr. BethAnn McLaughlin (committee member), Dr. Deborah Murdock (committee member), Dr. Brian Wadzinski (committee member).

Subjects/Keywords: Ischemic stroke; proteasome; HSP70; protein oxidation; mitophagy; mitochondrial permeability transition activities; CHIP; biotin-avidin-capture methodology

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

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

APA (6th Edition):

Stankowski, J. N. (2011). Role of C-terminus of HSC70 interacting protein in determining neuronal fate in acute injury. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://etd.library.vanderbilt.edu/available/etd-01242011-140331/ ;

Chicago Manual of Style (16th Edition):

Stankowski, Jeannette Nicole. “Role of C-terminus of HSC70 interacting protein in determining neuronal fate in acute injury.” 2011. Doctoral Dissertation, Vanderbilt University. Accessed November 12, 2019. http://etd.library.vanderbilt.edu/available/etd-01242011-140331/ ;.

MLA Handbook (7th Edition):

Stankowski, Jeannette Nicole. “Role of C-terminus of HSC70 interacting protein in determining neuronal fate in acute injury.” 2011. Web. 12 Nov 2019.

Vancouver:

Stankowski JN. Role of C-terminus of HSC70 interacting protein in determining neuronal fate in acute injury. [Internet] [Doctoral dissertation]. Vanderbilt University; 2011. [cited 2019 Nov 12]. Available from: http://etd.library.vanderbilt.edu/available/etd-01242011-140331/ ;.

Council of Science Editors:

Stankowski JN. Role of C-terminus of HSC70 interacting protein in determining neuronal fate in acute injury. [Doctoral Dissertation]. Vanderbilt University; 2011. Available from: http://etd.library.vanderbilt.edu/available/etd-01242011-140331/ ;

.