Sex specific effects of indomethacin-induced inflammatory bowel disease on mitochondrial function

Friday, April 22, 2022

Dr. Kristin Edwards

Assistant Professor, Department of Cell and Molecular Biology

University of Mississippi Medical Center

Friday, April 22nd 2022 at 3:30 PM in Hand 1144

Abstract: Inflammatory bowel disease (IBD) characterized by inflammation of the gastrointestinal tract. It includes Crohn’s disease and ulcerative colitis. In 2015, 3 million U.S. adults have been diagnosed with IBD and many people go undiagnosed due to mild symptoms. Women appear to have more severe and recurring symptoms of IBD compared to men, most likely due to hormonal fluctuations. Several studies show mitochondrial alterations in IBD patients. Our hypothesis is mitochondrial dysfunction in IBD could have a sex-specific effect. Male and female rats received two doses of indomethacin (7.5 mg/kg) 24 hour apart to induce IBD. Males showed no significant difference compared to controls with complex I and complex II-driven respiration. However, IBD females showed a significant decrease in Complex I-driven respiration and Complex II -driven respiration. For LCFA oxidation, males and females showed a significant increase in activity compared to controls. Both males and females showed no significant decrease MCFA oxidation. Males and females showed a significant increase in mtROS with all substrates. Complex IV activity was not different than controls in males but female activity was significantly decreased. Alterations to mitochondrial function and mitochondrial content observed in the indomethacin-induced IBD rat model suggests a link between mitochondrial dysfunction and IBD. There are differences in male and female rats suggesting a potential mechanism for the observed differences in male and female patients. Our study provides a better understanding of the role mitochondria in the development of IBD. It also opens an avenue for the development of strategies to re-establish normal mitochondrial function that could provide more options for preventive and therapeutic interventions for IBD.

Bio: Dr. Edwards received her BS degree in biology and chemistry from Jacksonville State University and her PhD in biochemistry from UMMC. Her PhD research focused on the mechanisms by which the echinocandin group of antifungal drugs affect mitochondrial bioenergetics. Her postdoctoral research focused on the deficiency of the mitochondrial inner membrane protein, uncoupling protein 3, and its impairment of cardiac energetics and contractile recovery following ischemia and reperfusion. Her work has led to various awards, including the APS- Cardiovascular Section Research Recognition Award. Dr. Edward’s current research focuses on the role of mitochondrial dysfunction associated with inflammatory bowel disease (IBD); the role of mitochondrial dysfunction in the comorbidities associated with IBD; and how mitochondrial targeted therapeutics are a treatment option for IBD and other human diseases.

Please join us for a reception with Dr. Edwards at 3:00 PM in Hand 1134.
Hosted by:  Dr. Nick Fitzkee

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