Mitogen-activated protein kinases in the acute diabetic myocardium.
Diabetes mellitus (DM) causes myocardial remodeling on the subcellular level and alterations in the function of the cell membranes ion transport systems resulting in contractile dysfunction. The present study was aimed to investigate the expression and activation of mitogen-activated protein kinases (MAPKs) and their possible role in the acute diabetic rat hearts. Rats were injected with single dose of streptozotocin (45 mg/kg, i.v.), and after 1 week the disease was manifested by hyperglycemia and cardiac dysfunction. The Langendorff-perfused hearts were subjected to ischemia (5 or 30 min occlusion of LAD coronary artery). The protein pattern in cytosolic fraction of the heart tissue was determined after electrophoretic separation. The levels and activation of MAPKs were determined by Western blot analysis using specific antibodies. No differences between the diabetics and controls in the level of ERKs were found at baseline. However, in DM samples ERKs phosphorylation was markedly increased, and further changes occurred during ischemia. Also content of phoshorylated c-Raf kinase (an upstream activator of ERKs) was slightly increased at baseline conditions in the diabetic samples. In contrast, no significant changes in the contents and phosphorylation of p38-MAPK were observed at baseline. But some differences in the p38-MAPK phosphorylation were found during ischemia. The results show that differential pattern of protein kinase cascades activation in the diabetic hearts might be account for the modulation of their response to ischemia.
Strniskova
Monika
M
Institute for Heart Research, Slovak Academy of Sciences, Bratislava, Slovak Republic. usrdmost@savba.sk
Barancik
Miroslav
M
Neckar
Jan
J
Ravingerova
Tanya
T
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D004195:Disease Models, Animal; D004789:Enzyme Activation; D007511:Ischemia; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism* / Q000502:physiology*; D009206:Myocardium / Q000201:enzymology*; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases
D001786:Blood Glucose; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases