Lay Summary

Proposal No. IBD-0226R
Principal Investigator: Shanthi V. Sitaraman, M.D., Ph.D.
Applicant Organization: Emory University (Atlanta, Georgia, U.S.A.)
Project Title: Prohibitin: a novel antioxidant based treatment for inflammatory bowel disease
Period of Award: January 1, 2009 – March 31, 2010

One of the factors that underlies inflammation and tissue damage in IBD is ‘reactive oxygen species (ROS)’. ROS are highly reactive derivatives of oxygen generated during inflammatory processes that can cause extensive tissue damage (termed oxidative stress). Oxidative stress is seen in majority of patients with active IBD wherein increased ROS and decreased enzymes that detoxify the ROS are seen. Thus preventing the generation of reactive oxygen species or increasing the detoxification of ROS is an effective means to treat IBD.

We have found that Prohibitin, a small protein found in the mitochondria (respiratory house of the cell), effectively combats oxidative stress. Interestingly, colonic tissue from patients with IBD has significantly reduced amounts of this protein. Forced expression of this protein in cells renders them resistant to oxidative stress and damage caused by oxidative stress. In this proposal, we will determine whether restoration of prohibitin will reverse oxidative damage. We will also demonstrate proof of principle for the use of prohibitin in the treatment of IBD by studying the susceptibility of mice engineered to produce excess prohibitin to colitis.

Significance: If successful, this project will establish prohibitin as a potential treatment for IBD-like diseases. If proven effective, prohibitin mimetic peptides will be a novel therapeutic option to treat IBD.