Age-related changes in oxidative capacity of the gastrocnemius muscle in normal and dystrophic ( [formula omitted]) mice

Abstract

The hind limb muscles of dy 2J dy 2J mice appear more oxidative than normal hind limb muscles when assayed histochemically. In some cases, biochemical assay of oxidative capacity does not match histochemical data, and in some dy 2J mice, particularly old animals, there appears to be a decline in biochemically assayed oxidative enzymes. The current study cyto-biochemically assayed succinic dehdrogenase activity of the gastrocnemius muscle in dy 2J and normal mice. The assays were conducted over a maturation time course of 1 to 6 months of age. Additionally, the gastrocnemius muscle was divided into two distinct regions, a superficial region, containing largely glycolytic fast-twitch fibers (SGM), and a deeper region of mixed, largely oxidative fibers (DGM) in normal animals. Assay of the whole muscle and the two regions of each individual muscle showed that the dy 2J muscle increased in SDH activity with maturation and was significantly greater than the change observed in normal muscle during the same period. The increase in the whole muscle SDH activity was accounted for increases noted in the SGM. The dy 2J DGM, which showed marked morphologic degeneration, had neither an increase nor a decrease in measured SDH activity. Michaelis-Menton analysis of the enzymatic assay indicated that the V max, and not the K m , of the dystrophic muscle enzyme system was higher than normal, suggesting a change in quantity of enzyme present, and not altered function of the system. The observed increases occurred for 4 months of maturation and then began a decline, which was noted at 6 months. Coupled with the time course of gastrocnemius muscle degeneration (the glycolytic region was slow—very little by 4 months; the mixed was fast—highly degenerated by 1 to 2 months), the results of this study suggest that oxidative capacity in the dy 2J gastrocnemius muscle increased with maturation until it became obscured by inherant muscle wasting in a particular dy 2J muscle region. By comparison, analysis of the large glycolytic triceps muscle, a forelimb muscle which does not receive pseudomyotonia, indicated that this muscle did not increase in SDH activity in dystrophic animals, which showed the abnormal increase in the activity of the hind limb gastrocnemius. Thus the relationship of pseudomyotonia to increasing oxidative activity in the hind limb muscles of dystrophic animals was evident.