The ubiquitin-proteasome proteolytic pathway in heart vs skeletal muscle: Effects of acute diabetes

The ubiquitin-proteasome system is thought to play a major role in normal m uscle protein turnover and to contribute to diabetes-induced protein wastin g in skeletal muscle. However, its importance in cardiac muscle is not clea r. We measured heart muscle mRNA for ubiquitin and for the C2 and C8 protea somal subunits, the amount of free ubiquitin and the proteasome chymotrypsi n-like proteolytic activity in control and diabetic rats. Results were comp ared to those in skeletal muscle (rectus). Heart ubiquitin, C2 and Cg subun it mRNA and proteolytic activity were significantly greater than in skeleta l muscle (P less than or equal to 0.05), This suggests that the ubiquitin p roteasomal pathway may also be important for normal heart muscle turnover. Diabetes increased ubiquitin mRNA by similar to 50% in heart (P < 0.03) and by similar to 100% in skeletal muscle (P < 0.005). It remained high after 3 days of insulin treatment in both tissues. C2 and C8 subunit mRNA did not change with diabetes or insulin treatment. Diabetes did not change the amo unt of free ubiquitin or the proteasomal (lactacystin-inhibitable) chymotry psin-like peptidase activity in heart or skeletal muscle. In conclusions, g ene expression for several components of the ubiquitin-proteasome proteolyt ic pathway is significantly higher in cardiac than in skeletal muscle, as i s the proteasome chymotrypsin-like peptidase activity. Diabetes increases t he expression of ubiquitin but not C2 or C8 subunit mRNA, nor does it signi ficantly alter the amount of free ubiquitin or the proteasome chymotrypsin- libe peptidase activity. The rate-limiting step of enhanced protein degrada tion in diabetic rat heart and skeletal muscle may be located at ubiquitin conjugation and/or its binding to proteasome, not at the ubiquitin availabi lity or the proteasome itself, (C) 2000 Academic Press.