Mitogen-activated protein kinases in the acute diabetic myocardium
Tóm tắt
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.
Tài liệu tham khảo
Haider B, Ahmed SS, Moschos CB, Oldewurtel HA, Regan TJ: Myocardial function and coronary blood flow response to acute ischemia in chronic canine diabetes. Circ Res 40: 577-583, 1977
Tani M, Neely JR: Hearts from diabetic rats are more resistant to in vitro ischemia: Possible role of altered Ca2+ metabolism. Circ Res 62: 931-940, 1988
Ravingerova T, Stetka R, Volkovova K, Pancza D, Dzurba A, Ziegelhöffer A, Styk J: Acute diabetes modulates response to ischemia in isolated rat heart. Mol Cell Biochem 210: 143-151, 2000
Barancik M, Htun P, Strohm C, Kilian S, Schaper W: Inhibition of the cardiac p38-MAPK pathway by SB203580 delays ischemic cell death. J Cardiovasc Pharmacol 35: 474-483, 2000
Sugden PH, Clerk A: 'stress-responsive' mitogen-activated protein kinases (c-Jun N-terminal kinases and p38 mitogen-activated protein kinases) in the myocardium. Circ Res 83: 345-352, 1998
Marais E, Genade S, Huisamen B, Strijdom JG, Moolman JA, Lochner A: Activation of p38 MAPK induced by a multi-cycle ischaemic preconditioning protocol is associated with attenuated p38 MAPK activity during sustained ischaemia and reperfusion. J Mol Cell Cardiol 33: 769-778, 2001
Ma XL, Kumar S, Gao F, Louden CS, Lopez BL, Christopher TA, Wang C, Lee JC, Feuerstein GZ, Yue TL: Inhibition of p38 mitogen-activated protein kinase decreases cardiomyocyte apoptosis and improves cardiac function after myocardial ischemia and reperfusion. Circulation 99: 1685-1691, 1999
Igarashi M, Wakasaki H, Takahara N, Ishii H, Jiang ZY, Yamauchi T, Kuboki K, Meier M, Rhodes CJ, King GL: Glucose or diabetes activates p38 mitogen-activated protein kinase via different pathways. J Clin Invest 103: 185-195, 1999
Parekh VV, Hoffman JL, Younoszai MK: Effect of diabetes and difluoromethylornithine treatment on hyperplasia, activity of MAP-kinase, and activity and association with cyclin B of p34cdc2 kinase in rat jejunal mucosa. J Invest Med 46: 76-81, 1998
Haneda M, Araki S, Togawa M, Sugimoto T, Isono M, Kikkawa R: Mitogen-activated protein kinase cascade is activated in glomeruli of diabetic rats and glomerular mesangial cells cultured under high glucose conditions. Diabetes 46: 847-853, 1997
Awazu M, Ishikura K, Hida M, Hoshiya M: Mechanisms of mitogen-activated protein kinase activation in experimental diabetes. J Am Soc Nephrol 10: 738-745, 1999
Ho FM, Liu SH, Liau CS, Huang PJ, Lin-Shiau SY: High glucose-induced apoptosis in human endothelial cells is mediated by sequential activation of c-Jun NH(2)-terminal kinase and caspase-3. Circulation 101: 2618-2624, 2000
Liu W, Schoenkerman A, Lowe WL Jr: Activation of members of the mitogen-activated protein kinase family by glucose in endothelial cells. Am J Physiol Endocrinol Metab 279: E782-E790, 2000
Clerk A, Bogoyevitch MA, Anderson MB, Sugden PH: Differential activation of protein kinase C isoforms by endothelin-1 and phenyl-epinephrine, and subsequent stimulation of p42 and p44 mitogen-activated protein kinases in ventricular myocytes cultured from neonatal rat hearts. J Biol Chem 269: 32848-32857, 1994
Foncea R, Anderson M, Ketterman A, Blakesley V, Sapag-Hagar M, Sugden PH, LeRoith D, Lavandero S: Insulin-like growth factor-I rapidly activates multiple signal transduction pathways in cultured rat cardiac myocytes. J Biol Chem 272: 19115-19124, 1997
Yamazaki T, Tobe K, Hoh E, Maemura K, Kaida T, Komuro I, Tamemoto H, Kadowaki T, Nagai R, Yazaki Y: Mechanical loading activates mitogen-activated protein kinase and S6 peptide kinase in cultured rat cardiac myocytes. J Biol Chem 268: 12069-12076, 1993
Rouse J, Cohen P, Trigon S, Morange M, Alonso-Llamazares A, Zamanillo D, Hunt T, Nebreda AR: A novel kinase cascade triggered by stress and heat shock that stimulates MAPKAP kinase-2 and phosphorylation of the small heat shock proteins. Cell 78: 1027-1037, 1994
Raingeaud J, Gupta S, Rogers JS, Dickens M, Han J, Ulevitch RJ, Davis RJ: Pro-inflammatory cytokines and environmental stress cause p38 mitogen-activated protein kinase activation by dual phosphorylation on tyrosine and threonine. J Biol Chem 270: 7420-7426, 1995
Iordanov MS, Pribnow D, Magun JL, Dinh TH, Pearson JA, Magun BE: Ultraviolet radiation triggers the ribotoxic stress response in mammalian cells. J Biol Chem 273: 15794-15803, 1998
Yuasa T, Ohno S, Kehrl JH, Kyriakis JM: Tumor necrosis factor signaling to stress-activated protein kinase (SAPK)/Jun NH2-terminal kinase (JNK) and p38: Germinal center kinase couples TRAF2 to mitogen-activated protein kinase/ERK kinase kinase 1 and SAPK while receptor interacting protein associates with a mitogen-activated protein kinase kinase kinase upstream of MKK6 and p38. J Biol Chem 273: 22681-22692, 1998
Bandyopadhyay G, Sajan MP, Kanoh Y, Standaert ML, Burke TR Jr, Quon MJ, Reed BC, Dikic I, Nocl LE, Newgard CB, Farese R: Glucose activates mitogen-activated protein kinase (extracellular signal-regulated kinase) through proline-rich tyrosine kinase-2 and the Glut 1 glucose transporter. J Biol Chem 275: 40817-40826, 2000
Haneda M, Kikkawa R, Sugimoto T, Koya D, Araki S, Togawa M, Shigeta Y: Abnormalities in protein kinase C and MAP kinase cascade in mesangial cells cultured under high glucose conditions. J Diabetes Complications 9: 246-248, 1995
Bandyopadhyay G, Sajan MP, Kanoh Y, Standaert ML, Quon MJ, Reed BC, Dikic I, Farese RV: Glucose activates protein kinase C-zeta/lambda through proline-rich tyrosine kinase-2, extracellular signal-regulated kinase, and phospholipase D: A novel mechanism for activating glucose transporter translocation. J Biol Chem 276: 35537-35545, 2001
Tomlinson DR: Mitogen-activated protein kinases as glucose transducers for diabetic complications. Diabetologia 42: 1271-1281, 1999
Kang MJ, Wu X, Ly H, Thai K, Scholey JW: Effect of glucose on stress-activated protein kinase activity in mesangial cells and diabetic glomeruli. Kidney Int 55: 2203-2214, 1999
Fernyhough P, Gallagher A, Averill SA, Priestley JV, Hounsom L, Patel J, Tomlinson DR: Aberrant neurofilament phosphorylation in sensory neurons of rats with diabetic neuropathy. Diabetes 48: 881-889, 1999
Dunlop ME, Muggli EE: Small heat shock protein alteration provides a mechanism to reduce mesangial cell contractility in diabetes and oxidative stress. Kidney Int 57: 464-475, 2000
Kikkawa R: Chronic complications in diabetes mellitus. Br J Nutrition 84Suppl 2: S183-S185, 2000
Ping P, Zhang J, Cao X, Li RC, Kong D, Tang XL, Qiu Y, Manchikalapudi S, Auchampach JA, Black RG, Bolli R: PKC-dependent activation of p44/p42 MAPKs during myocardial ischemia-reperfusion in conscious rabbits. Am J Physiol Heart Circ Physiol 276: H1468-H1481, 1999
Strohm C, Barancik M, v.Brühl ML, Kilian SAR, Schaper W: Inhibiton of the ER-Kinase by PD98059 and UO126 counteracts ischemic preconditioning in pig myocardium. J Cardiovasc Pharmacol 36: 218-229, 2000
Kuwahara K, Saito Y, Kishimoto I, Miyamoto Y, Harada M, Ogawa E, Hamanaka I, Kajiyama N, Takahashi N, Izumi T, Kawakami R, Nakao K: Cardiotrophin-1 phosphorylates Akt and BAD, and prolongs cell survival via a PI3K-dependent pathway in cardiac myocytes. J Mol Cell Cardiol 32: 1385-1394, 2000
Bogoyevitch MA, Gillespie-Brown J, Ketterman AJ, Fuller SJ, Ben-Levy R, Ashworth A, Marshall CJ, Sugden PH: Stimulation of the stress-activated mitogen-activated protein kinases subfamilies in perfused heart. p38/RK mitogen-activated protein kinases and c-jun N-terminal kinases are activated by ischemia/reperfusion. Circ Res 79: 162-173, 1996
Knight RJ, Buxton DB: Stimulation of c-Jun kinase and mitogen-activated protein kinase by ischemia and reperfusion in the perfused rat hearts. Biochem Biophys Res Commun 218: 83-88, 1996
Behrends M, Schulz R, Post H, Alexandrov A, Belosjorow S, Michel MC, Heusch G: Inconsistent relation of MAPK activation to infarct size reduction by ischemic preconditioning in pigs. Am J Physiol Heart Circ Physiol 279: H1111-H1119, 2000
Shimizu N, Yoshiyama M, Omura T, Hanatani A, Kim S, Takeuchi K, Iwao H, Yoshikawa J: Activation of mitogen-activated protein kinases and activator protein-1 in myocardial infarction in rats. Cardiovasc Res 38: 116-124, 1998