Prohibitin (PHB) is implicated to be involved in diverse cellular processes such as oxidative stress. The expression and function of PHB in the normal intestine and during intestinal inflammation are not known. Oxidative stress plays an important role in the pathogenesis of inflammatory bowel diseases due to its effects on mucosal barrier disruption and inflammation. Given the potential role of PHB in regulating oxidative stress during various physiological conditions, PHB may be involved in modulating oxidative stress associated with intestinal inflammation. The overall goal of this proposal is to characterize the regulation of PHB in intestinal epithelial cells and its role in modulating inflammation-induced oxidative stress and wound healing. The regulation of PHB expression by the immunoregulatory cytokine IL-6 will be studied. The role of PHB in oxidative stress and wound healing will be determined using an intestinal epithelial cell line over- or under-expressing PHB. Also, the in vivo effect of IL-6 knockout on PHB expression and wound healing will be assessed during experimental colitis. Thus, studies on PHB will lead to a better understanding of inflammation-induced oxidative stress and may lead to novel therapies for intestinal inflammatory disorders. ? ? ?

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 #
5F32DK076243-03
Application #
7477917
Study Section
Special Emphasis Panel (ZRG1-F10-H (22))
Program Officer
Podskalny, Judith M,
Project Start
2006-09-01
Project End
2009-08-31
Budget Start
2008-09-01
Budget End
2009-08-31
Support Year
3
Fiscal Year
2008
Total Cost
$50,428
Indirect Cost
Name
Emory University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Theiss, Arianne L; Laroui, Hamed; Obertone, Tracy S et al. (2011) Nanoparticle-based therapeutic delivery of prohibitin to the colonic epithelial cells ameliorates acute murine colitis. Inflamm Bowel Dis 17:1163-76
Theiss, Arianne L; Vijay-Kumar, Matam; Obertone, Tracy S et al. (2009) Prohibitin is a novel regulator of antioxidant response that attenuates colonic inflammation in mice. Gastroenterology 137:199-208, 208.e1-6
Theiss, Arianne L; Jenkins, Aaron K; Okoro, Ngozi I et al. (2009) Prohibitin inhibits tumor necrosis factor alpha-induced nuclear factor-kappa B nuclear translocation via the novel mechanism of decreasing importin alpha3 expression. Mol Biol Cell 20:4412-23
Theiss, Arianne L; Obertone, Tracy S; Merlin, Didier et al. (2007) Interleukin-6 transcriptionally regulates prohibitin expression in intestinal epithelial cells. J Biol Chem 282:12804-12