Relationship between NADP-specific isocitrate dehydrogenase and glutathione peroxidase in aging rat skeletal muscle.

The glutathione peroxidase (GPX) system detoxifies hydroperoxides in cells and uses NADPH to regenerate reduced glutathione. Enzymatic sources of NADPH in skeletal muscle include NADP-specific isocitrate dehydrogenase (ICDP), glucose-6-phosphate dehydrogenase (G6PD), and malic enzyme (ME). Our purpose was to explore the relationship in skeletal muscle between GPX and ICDP along with other NADPH-generating enzymes as a function of progressive age and muscle fiber-type. Soleus (SOL), red gastrocnemius (RG), and white gastrocnemius (WG) muscles were extracted from Fischer-344 rats of three different ages: 4 months old (Y); 18 months old (M); and 24 months old (O). Assays were conducted to determine activities of GPX, ICDP, G6PD, and ME along with levels of lipid hydroperoxides. GPX activities were significantly greater in RG and WG of old rats than in younger. ICDP activities were higher in the WG of old and middle aged rats when compared to young adults. GPX and ICDP activities exhibited similar differences among the muscles tested (SOL>RG>WG). In contrast, G6PD and ME activities were not significantly different across muscles. G6PD activities increased in RG with age, but were well over an order of magnitude lower than ICDP in all muscles. ME activities were universally lower than ICDP in all muscles, and decreased with old age in the WG and RG. Lipid hydroperoxides were significantly higher with aging in RG. Significant correlations were found between GPX and ICDP in all muscles. Stepwise regression resulted in a model (R(2)=0.82) that included ICDP and ME in predicting GPX. In summary, these data are consistent with the hypotheses that ICDP is higher in more oxidative fibers, inducible with aging, and most closely associated with the glutathione peroxidase system in skeletal muscle.