MODULATION OF RAT-HEART MITOCHONDRIAL-FUNCTION AND THE PRODUCTION OF REACTIVE OXYGEN BY VITAMIN-E-DEFICIENCY

Vitamin E, an antioxidant present in all cellular membranes, is associated with protein complexes in the inner mitochondrial membranes and may affect oxidative changes which occur in these organelles when heart tissue is subjected to hypoxia. The effect of 60 min hypoxia, after a 30 min normoxic equilibration period, on the function and the production of reactive oxygen species (ROS) by cardiac mitochondria from rats fed vitamin E sufficient or deficient diets for 9 weeks was examined. Mitochondria from the hearts of rats fed vitamin E deficient diets had 40-fold less vitamin E and were more susceptible to lipid peroxidation, as compared to heart mitochondria from rats fed vitamin E sufficient diet. Perfusion with normoxic, but not hypoxic, media significantly decreased cardiac vitamin E in deficient, but not sufficient rats. Hypoxia decreased the production of ROS by mitochondria from vitamin E sufficient hearts, compared to normoxia. A similar level of ROS production was seen after hypoxia in mitochondria from vitamin E deficient hearts. However, vitamin E deficiency alone decreased the production of ROS by mitochondria from normoxic hearts, relative to vitamin E sufficient animals. Under all conditions where the production of ROS was decreased, 1 mu M calcium increased production to the maximum levels seen in vitamin E sufficient, normoxic heart mitochondria. Mitochondrial function was depressed in mitochondria from hypoxic hearts as compared to mitochondria from normoxic hearts of vitamin E sufficient rats. A similar depression of mitochondrial function was not seen in mitochondria from hypoxic hearts of vitamin E deficient rats. Compensatory changes in response to long-term vitamin E deficiency may be responsible for the differences in response to hypoxia of mitochondria from vitamin E sufficient and deficient rats.