A critical event that activates caspases and induces apoptosis in mammalian cells is the release of cytochrome c from the mitochondria into the cytosol. However, our preliminary data indicate that while endogenous release of cytochrome c can readily induce apoptosis in mitotic cells, it is not sufficient to do so in sympathetic neurons. In addition, we find levels of cytochrome c protein, but interestingly not levels of cytochrome c mRNA, to be strikingly low in neurons as compared to mitotic fibroblasts. Our hypothesis is that a sympathetic neuron's resistance to the endogenous release of cytochrome c is due to low levels of cytochrome c in neurons.
The aims of this proposal are: 1) to examine whether cytochrome c levels are limiting for apoptosis in neurons, and determine if they increase in response to apoptotic stimuli. 2) to test the hypothesis that SM-20 (which is induced in apoptotic neurons) is to increase cytochrome c levels to permit apoptosis in neurons. 3) to ask whether the differential expression of cytochrome c seen in mitotic cells and postmitotic neurons is a result of decreased translation or increased protein turnover in sympathetic neurons. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
1F31NS055486-01A1
Application #
7222939
Study Section
Special Emphasis Panel (ZRG1-F03A-M (20))
Program Officer
Golanov, Eugene V
Project Start
2006-12-22
Project End
2008-12-21
Budget Start
2006-12-22
Budget End
2007-12-21
Support Year
1
Fiscal Year
2007
Total Cost
$26,639
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Physiology
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599