Changes in cardiac protein kinase C activities and isozymes in streptozotocin-induced diabetes.
To understand cardiac dysfunction in diabetes, the activity of protein kinase C (PKC) and protein contents of its isozymes (PKC-alpha, -beta, -epsilon, and -zeta) were examined in diabetic rats upon injection of streptozotocin (65 mg/kg iv). The hearts were removed at 1, 2, 4, and 8 wk, and some of the 6-wk diabetic animals had been injected with insulin (3 U/day) for 2 wk. The Ca(2+)-dependent PKC activity was increased by 43 and 51% in the homogenate fraction and 31 and 70% in the cytosolic fraction from the 4- and 8-wk diabetic hearts, respectively, in comparison with control values. The Ca(2+)-independent PKC activity was increased by 24 and 32% in the homogenate fraction and 52 and 89% in the cytosolic fraction from the 4- and 8-wk diabetic hearts, respectively, in comparison with control values. The relative protein contents of PKC-alpha, -beta, -epsilon, and -zeta isozymes were increased by 43, 31, 48, and 38%, respectively, in the homogenate fraction and by 126, 119, 148, and 129%, respectively, in the cytosolic fraction of the 8-wk diabetic heart. The observed changes in heart homogenate and cytosolic fractions were partially reversible upon treatment of the diabetic rats with insulin. The results suggest that the increased myocardial PKC activity and increased protein contents of the cytosolic PKC isozymes are associated with subcellular alterations and cardiac dysfunction in the diabetic heart.
Liu
X
X
Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba R2H 2A6, Canada.
Wang
J
J
Takeda
N
N
Binaglia
L
L
Panagia
V
V
Dhalla
N S
NS
D000818:Animals; D009202:Cardiomyopathies / Q000378:metabolism*; D002462:Cell Membrane / Q000201:enzymology; D003600:Cytosol / Q000201:enzymology; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007527:Isoenzymes / Q000032:analysis / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D011493:Protein Kinase C / Q000032:analysis / Q000378:metabolism*; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha; D051744:Protein Kinase C-epsilon; D051381:Rats; D017207:Rats, Sprague-Dawley; D013347:Subcellular Fractions / Q000201:enzymology; D000099221:Protein Kinase C zeta
D007004:Hypoglycemic Agents; D007328:Insulin; D007527:Isoenzymes; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha; D051744:Protein Kinase C-epsilon; D000099221:Protein Kinase C zeta; C497257:Prkce protein, rat