REGULATION OF MUSCLE PROTEOLYSIS: INTERRELATIONSHIPS WITH THE NAD, NADP, AND GLUTATHIONE REDOX COUPLES.

The mechanisms by which hormones and metabolites control muscle proteolysis remain unclear. The redox state of muscle has been investigated as a possible mediator of these effects. In diaphragms of traumatized and starved animals, faster proteolysis correlated with a more oxidized NAD(P) redox couple. In diaphragm, leucine lowered proteolysis and increased lactate/pyruvate ratios. The soleus and extensor digitorum longus (EDL) muscles from young growing rats had faster proteolysis and lower lactate/pyruvate ratios than of older rats. The lower proteolysis and high lactate/pyruvate ratios in larger muscles from older rats are not due to experimental oxygen diffusion limitations, but are probably inherent characteristics of the muscles themselves. Proteolysis, and medium and incubated tissue lactate/pyruvate ratios gave significant multiple correlations with the soleus (R = 0.939) and EDL (R = 0.973) weights. Up to four days of streptozotocin diabetes, the lactate/pyruvate ratios were lower and proteolysis was faster in soleus and EDL muscles compared to weight matched controls. Conversely, after six to 12 days, proteolysis was lower and lactate/pyruvate ratios were higher. In EDL of young fasted rats accelerated proteolysis was associated with lower lactate/pyruvate ratios. In older rats, proteolysis increased and lactate/pyruvate ratios decreased during short-term fasting. The reverse was true following long-term fasting, indicating a "protein-sparing" effect. In contrast, the soleus showed little change in redox state and proteolysis during starvation. Concentrations of reduced, oxidized and protein-bound glutathione were measured in normal, diabetic and fasting rats to determine whether the glutathione redox couple responded similarly to the NAD(P) redox couple. In muscles from fasted and diabetic rats decreases in reduced glutathione content lowered the reduced/oxidized glutathione ratio. The relationship between proteolysis and the glutathione redox state, however, was not strong. Likewise, incubations with insulin of leg muscles of fed, fasted, and diabetic muscles, decreased proteolysis but affected little the NAD and glutathione redox couples. Generally, in muscle accelerated proteolysis was associated with an oxidation of the NAD(P) redox couple and vice versa. These data suggest that, in muscle, the redox state may be important in the regulation of proteolysis