The purpose of this research proposal is to investigate mechanisms involved in the Shiga toxin 2 induced apoptosis in the human kidney epithelial cell line HK-2. Infection with Shiga toxin producing E. coli may lead to the development of bloody diarrhea and hemolytic-uremic syndrome (HUS). The development of HUS has been attributed to Shiga toxin induced renal tissue injury. Shiga toxins are known to inhibit eukaryotic protein synthesis and cause cell death by apoptosis or necrosis. To investigate Shiga toxin induced apoptosis we propose to examine the phosphorylation of the anti-apoptotic Bcl-2 family members Bcl-2 and BcI-XL. In many cell systems these phosphorylation events are associated with the inhibition of the antiapoptotic function of these proteins and may lead to cell death. In addition, we also propose to examine the phosphorylation status and trafficking of the pro-apoptotic protein Bad, which when dephosphorylated, undergoes transport from the cytoplasm to the mitochondria to induce apoptosis. Finally, since Shiga toxins can inhibit protein synthesis, we wish to examine if Shiga toxin interferes with mRNA transcript stability and translation of a variety of pro- and anti-apoptotic genes as a novel mechanism of apoptosis regulation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32DK064536-03
Application #
6999757
Study Section
Special Emphasis Panel (ZRG1-F08 (20))
Program Officer
Rankin, Tracy L
Project Start
2004-04-09
Project End
2007-04-09
Budget Start
2005-04-10
Budget End
2006-04-09
Support Year
3
Fiscal Year
2005
Total Cost
$49,928
Indirect Cost
Name
University of Maryland Baltimore
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
188435911
City
Baltimore
State
MD
Country
United States
Zip Code
21201
Nougayrede, Jean-Philippe; Foster, Gregory H; Donnenberg, Michael S (2007) Enteropathogenic Escherichia coli effector EspF interacts with host protein Abcf2. Cell Microbiol 9:680-93