EFFECTS OF METHIONINE RESTRICTION ON GLUTATHIONE RELATED PATHWAYS
Open Access
- Author:
- Maddineni, Sreenivasa
- Graduate Program:
- Laboratory Animal Medicine
- Degree:
- Master of Science
- Document Type:
- Master Thesis
- Date of Defense:
- None
- Committee Members:
- Dr. John P. Richie, Jr, Thesis Advisor/Co-Advisor
- Keywords:
- Methionine restriction
GSH
GPX
GR - Abstract:
- The tripeptide glutathione (GSH) is the principal antioxidant in cells and its depletion is associated with the onset of age-related chronic diseases including cardiovascular disease, cancer, Parkinson’s disease, atherosclerosis, chronic fatigue syndrome, and nuclear cataract. Dietary methionine restriction (0.17% methionine, MR) has been found to enhance longevity in rats and mice independent of energy restriction and have differential effects on GSH levels in liver, kidney and blood. We hypothesized that MR is specifically affecting GSH metabolism and transport as a result of reduced tissue availability of sulfur amino acids precursors and reduced levels of oxidative stress. To test this hypothesis, male Fischer 344 rats were fed control (0.86% methionine) or MR (0.17% methionine) diets for 4 weeks or 6 months, and GSH and its key redox-enzymes were analyzed at various time points. In the 4 wk study, blood GSH levels increased and liver and kidney GSH levels decreased in MR rats compared to control rats. GSH peroxidase activities are reduced in livers of MR rats in both 4 wk and 6 month study. GSH reductase activity increased only in liver but not in the kidney and brain at 4 wks. However, there are no differences observed in GSH reductase activity in all organs in the 6 month study. These results from the study indicate that MR is associated with GSH peroxidase activity and GSH levels, and increased GSSG reductase activity in the liver. Thus, the depletion of GSH by MR in the liver does not appear to be a result of changes in its redox pathway. Because of the decreased levels of oxidative stress, the requirement of GSH in the liver may be reduced.