Liu Z, Miers W R, Wei L, Barrett E J
Division of Endocrinology and Metabolism, University of Virginia Health Sciences Center, Charlottesville, Virginia, 22908, USA.
Biochem Biophys Res Commun. 2000 Oct 5;276(3):1255-60. doi: 10.1006/bbrc.2000.3609.
The ubiquitin-proteasome system is thought to play a major role in normal muscle protein turnover and to contribute to diabetes-induced protein wasting in skeletal muscle. However, its importance in cardiac muscle is not clear. We measured heart muscle mRNA for ubiquitin and for the C2 and C8 proteasomal subunits, the amount of free ubiquitin and the proteasome chymotrypsin-like proteolytic activity in control and diabetic rats. Results were compared to those in skeletal muscle (rectus). Heart ubiquitin, C2 and C8 subunit mRNA and proteolytic activity were significantly greater than in skeletal muscle (P </= 0.05). This suggests that the ubiquitin proteasomal pathway may also be important for normal heart muscle turnover. Diabetes increased ubiquitin mRNA by approximately 50% in heart (P < 0.03) and by approximately 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 amount of free ubiquitin or the proteasomal (lactacystin-inhibitable) chymotrypsin-like peptidase activity in heart or skeletal muscle. In conclusions, gene expression for several components of the ubiquitin-proteasome proteolytic pathway is significantly higher in cardiac than in skeletal muscle, as is the proteasome chymotrypsin-like peptidase activity. Diabetes increases the expression of ubiquitin but not C2 or C8 subunit mRNA, nor does it significantly alter the amount of free ubiquitin or the proteasome chymotrypsin-like peptidase activity. The rate-limiting step of enhanced protein degradation in diabetic rat heart and skeletal muscle may be located at ubiquitin conjugation and/or its binding to proteasome, not at the ubiquitin availability or the proteasome itself.
泛素 - 蛋白酶体系统被认为在正常肌肉蛋白质周转中起主要作用，并导致糖尿病引起的骨骼肌蛋白质消耗。然而，其在心肌中的重要性尚不清楚。我们测量了对照和糖尿病大鼠心肌中泛素、C2和C8蛋白酶体亚基的mRNA、游离泛素的量以及蛋白酶体类胰凝乳蛋白酶的蛋白水解活性。将结果与骨骼肌（腹直肌）的结果进行比较。心脏泛素、C2和C8亚基mRNA以及蛋白水解活性显著高于骨骼肌（P≤0.05）。这表明泛素蛋白酶体途径可能对正常心肌周转也很重要。糖尿病使心脏中泛素mRNA增加约50%（P<0.03），使骨骼肌中泛素mRNA增加约100%（P<0.005）。在两个组织中胰岛素治疗3天后其仍保持高水平。C2和C8亚基mRNA在糖尿病或胰岛素治疗后没有变化。糖尿病未改变心脏或骨骼肌中游离泛素的量或蛋白酶体（可被乳胞素抑制）类胰凝乳蛋白酶的肽酶活性。总之，泛素 - 蛋白酶体蛋白水解途径的几个组分的基因表达在心脏中显著高于骨骼肌，蛋白酶体类胰凝乳蛋白酶的肽酶活性也是如此。糖尿病增加泛素的表达，但不增加C2或C8亚基mRNA的表达，也不显著改变游离泛素的量或蛋白酶体类胰凝乳蛋白酶的肽酶活性。糖尿病大鼠心脏和骨骼肌中蛋白质降解增强的限速步骤可能位于泛素缀合和/或其与蛋白酶体的结合，而不是泛素的可用性或蛋白酶体本身。
