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 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.
Liu
Z
Z
Division of Endocrinology and Metabolism, University of Virginia Health Sciences Center, Charlottesville, Virginia, 22908, USA.
Miers
W R
WR
Wei
L
L
Barrett
E J
EJ
D000208:Acute Disease; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D002918:Chymotrypsin / Q000235:genetics / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology; D008297:Male; D009097:Multienzyme Complexes / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D009929:Organ Size; D046988:Proteasome Endopeptidase Complex; D021122:Protein Subunits; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014452:Ubiquitins / Q000235:genetics / Q000378:metabolism*
D001786:Blood Glucose; D007328:Insulin; D009097:Multienzyme Complexes; D021122:Protein Subunits; D012333:RNA, Messenger; D014452:Ubiquitins; D002918:Chymotrypsin; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex