Relationship of the redox state to muscle protein degradation

With increasing muscle size, incubated or fresh-frozen leg muscles showed a more reduced redox state and slower proteolysis. The ln of these data gave a linear correlation showing faster proteolysis under more oxidized conditions. In incubated diaphragms, the inhibitory effects of insulin and catecholamines on proteolysis were associated with a more reduced state. Fasting, trauma or cortisol treatment led to accelerated proteolysis and a more oxidized state. Long term fasting and refeeding supported this relationship, as did streptozotocin diabetes. Like the NAD+ and NADP+ redox couples, the glutathione couple seemed to fit this relationship. Use of proteinase inhibitors showed that the redox state probably mediated the effects of the various factors on proteolysis rather than vice versa. Muscle contains thioltransferase which catalyzes the formation of glutathione-protein mixed disulfides. We propose that increased formation of oxidized glutathione and its interaction with muscle proteins may act as a signal for the initiation of proteolysis.