© 1996 American Heart Association, Inc.
Articles |
Stimulation of the Stress-Activated Mitogen-Activated Protein Kinase Subfamilies in Perfused Heart
p38/RK Mitogen-Activated Protein Kinases and c-Jun N-Terminal Kinases Are Activated by Ischemia/Reperfusion
the National Heart and Lung Institute (Cardiac Medicine), Imperial College of Science, Technology, and Medicine, and the Section of Cell and Molecular Biology, Chester Beatty Laboratories, Institute of Cancer Research, University of London (UK).
Correspondence to Dr Peter H. Sugden, Cardiac Medicine, National Heart and Lung Institute, Dovehouse Street, London SW3 6LY, UK.
It has recently been recognized that cellular stresses activate certain members of the mitogen-activated protein kinase (MAPK) superfamily. One role of these "stress-activated" MAPKs is to increase the transactivating activity of the transcription factors c-Jun, Elk1, and ATF2. These findings may be particularly relevant to hearts that have been exposed to pathological stresses. Using the isolated perfused rat heart, we show that global ischemia does not activate the 42- and 44-kD extracellular signal–regulated (protein) kinase (ERK) subfamily of MAPKs but rather stimulates a 38-kD activator of MAPK-activated protein kinase-2 (MAPKAPK2). This activation is maintained during reperfusion. The molecular characteristics of this protein kinase suggest that it is a member of the p38/reactivating kinase (RK) group of stress-activated MAPKs. In contrast, stress-activated MAPKs of the c-Jun N-terminal kinase (JNK/SAPKs) subfamily are not activated by ischemia alone but are activated by reperfusion following ischemia. Furthermore, transfection of ventricular myocytes with activated protein kinases (MEKK1 and SEK1) that may be involved in the upstream activation of JNK/SAPKs induces increases in myocyte size and transcriptional changes typical of the hypertrophic response. We speculate that activation of multiple parallel MAPK pathways may be important in the responses of hearts to cellular stresses.
Key Words: mitogen-activated protein kinase • stress-activated mitogen-activated protein kinase • c-Jun N-terminal kinase • p38/reactivating kinase • ischemia/reperfusion
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G. Vassort Adenosine 5'-Triphosphate: a P2-Purinergic Agonist in the Myocardium Physiol Rev, April 1, 2001; 81(2): 767 - 806. [Abstract] [Full Text] [PDF]
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J. M. Kyriakis and J. Avruch Mammalian Mitogen-Activated Protein Kinase Signal Transduction Pathways Activated by Stress and Inflammation Physiol Rev, April 1, 2001; 81(2): 807 - 869. [Abstract] [Full Text] [PDF]
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 D. Hreniuk, M. Garay, W. Gaarde, B. P. Monia, R. A. McKay, and C. L. Cioffi Inhibition of C-Jun N-Terminal Kinase 1, but Not c-Jun N-Terminal Kinase 2, Suppresses Apoptosis Induced by Ischemia/Reoxygenation in Rat Cardiac Myocytes Mol. Pharmacol., April 1, 2001; 59(4): 867 - 874. [Abstract] [Full Text]
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K. Yamashita, J. Kajstura, D. J. Discher, B. J. Wasserlauf, N. H. Bishopric, P. Anversa, and K. A. Webster Reperfusion-Activated Akt Kinase Prevents Apoptosis in Transgenic Mouse Hearts Overexpressing Insulin-Like Growth Factor-1 Circ. Res., March 30, 2001; 88(6): 609 - 614. [Abstract] [Full Text] [PDF]
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C. Beauloye, L. Bertrand, U. Krause, A.-S. Marsin, T. Dresselaers, F. Vanstapel, J.-L. Vanoverschelde, and L. Hue No-Flow Ischemia Inhibits Insulin Signaling in Heart by Decreasing Intracellular pH Circ. Res., March 16, 2001; 88(5): 513 - 519. [Abstract] [Full Text] [PDF]
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T. C. Zhao, D. S. Hines, and R. C. Kukreja Adenosine-induced late preconditioning in mouse hearts: role of p38 MAP kinase and mitochondrial KATP channels Am J Physiol Heart Circ Physiol, March 1, 2001; 280(3): H1278 - H1285. [Abstract] [Full Text] [PDF]
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S. Schneider, W. Chen, J. Hou, C. Steenbergen, and E. Murphy Inhibition of p38 MAPK {alpha}/{beta} reduces ischemic injury and does not block protective effects of preconditioning Am J Physiol Heart Circ Physiol, February 1, 2001; 280(2): H499 - H508. [Abstract] [Full Text] [PDF]
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O. F. Bueno, L. J. De Windt, H. W. Lim, K. M. Tymitz, S. A. Witt, T. R. Kimball, and J. D. Molkentin The Dual-Specificity Phosphatase MKP-1 Limits the Cardiac Hypertrophic Response In Vitro and In Vivo Circ. Res., January 19, 2001; 88(1): 88 - 96. [Abstract] [Full Text] [PDF]
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 S. Tinton and P. B. Calderon Role of Protein Phosphorylation in the Inhibition of Protein Synthesis Caused by Hypoxia in Rat Hepatocytes International Journal of Toxicology, January 1, 2001; 20(1): 21 - 27. [Abstract] [PDF]
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S. Ghosh, L. L Ng, S. Talwar, I. B Squire, and M. Galinanes Cardiotrophin-1 protects the human myocardium from ischemic injury: Comparison with the first and second window of protection by ischemic preconditioning Cardiovasc Res, December 1, 2000; 48(3): 440 - 447. [Abstract] [Full Text] [PDF]
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 A. T. SAURIN, J. L. MARTIN, R. J. HEADS, C. FOLEY, J. W. MOCKRIDGE, M. J. WRIGHT, Y. WANG, and M. S. MARBER The role of differential activation of p38-mitogen-activated protein kinase in preconditioned ventricular myocytes FASEB J, November 1, 2000; 14(14): 2237 - 2246. [Abstract] [Full Text]
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S. Okubo, N. L. Bernardo, G. T. Elliott, M. L. Hess, and R. C. Kukreja Tyrosine kinase signaling in action potential shortening and expression of HSP72 in late preconditioning Am J Physiol Heart Circ Physiol, November 1, 2000; 279(5): H2269 - H2276. [Abstract] [Full Text] [PDF]
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M. Sato, G. A. Cordis, N. Maulik, and D. K. Das SAPKs regulation of ischemic preconditioning Am J Physiol Heart Circ Physiol, September 1, 2000; 279(3): H901 - H907. [Abstract] [Full Text] [PDF]
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M. Behrends, R. Schulz, H. Post, A. Alexandrov, S. Belosjorow, M. C. Michel, and G. Heusch Inconsistent relation of MAPK activation to infarct size reduction by ischemic preconditioning in pigs Am J Physiol Heart Circ Physiol, September 1, 2000; 279(3): H1111 - H1119. [Abstract] [Full Text] [PDF]
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J. W. Mockridge, A. Punn, D. S. Latchman, M. S. Marber, and R. J. Heads PKC-dependent delayed metabolic preconditioning is independent of transient MAPK activation Am J Physiol Heart Circ Physiol, August 1, 2000; 279(2): H492 - H501. [Abstract] [Full Text] [PDF]
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A. Dana, M. Skarli, J. Papakrivopoulou, and D. M. Yellon Adenosine A1 Receptor Induced Delayed Preconditioning in Rabbits : Induction of p38 Mitogen-Activated Protein Kinase Activation and Hsp27 Phosphorylation via a Tyrosine Kinase- and Protein Kinase C-Dependent Mechanism Circ. Res., May 12, 2000; 86(9): 989 - 997. [Abstract] [Full Text] [PDF]
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D. Talmor, A. Applebaum, A. Rudich, Y. Shapira, and A. Tirosh Activation of Mitogen-Activated Protein Kinases in Human Heart During Cardiopulmonary Bypass Circ. Res., May 12, 2000; 86(9): 1004 - 1007. [Abstract] [Full Text] [PDF]
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Y. J. Kang, Z.-X. Zhou, G.-W. Wang, A. Buridi, and J. B. Klein Suppression by Metallothionein of Doxorubicin-induced Cardiomyocyte Apoptosis through Inhibition of p38 Mitogen-activated Protein Kinases J. Biol. Chem., April 28, 2000; 275(18): 13690 - 13698. [Abstract] [Full Text] [PDF]
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H. Tong, W. Chen, R. E. London, E. Murphy, and C. Steenbergen Preconditioning Enhanced Glucose Uptake Is Mediated by p38 MAP Kinase Not by Phosphatidylinositol 3-Kinase J. Biol. Chem., April 14, 2000; 275(16): 11981 - 11986. [Abstract] [Full Text] [PDF]
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L. Faccio, A. Chen, C. Fusco, S. Martinotti, J. V. Bonventre, and A. S. Zervos Mxi2, a splice variant of p38 stress-activated kinase, is a distal nephron protein regulated with kidney ischemia Am J Physiol Cell Physiol, April 1, 2000; 278(4): C781 - C790. [Abstract] [Full Text] [PDF]
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T.-L. Yue, C. Wang, J.-L. Gu, X.-L. Ma, S. Kumar, J. C. Lee, G. Z. Feuerstein, H. Thomas, B. Maleeff, and E. H. Ohlstein Inhibition of Extracellular Signal-Regulated Kinase Enhances Ischemia/Reoxygenation-Induced Apoptosis in Cultured Cardiac Myocytes and Exaggerates Reperfusion Injury in Isolated Perfused Heart Circ. Res., March 31, 2000; 86(6): 692 - 699. [Abstract] [Full Text] [PDF]
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M. A. Bogoyevitch Signalling via stress-activated mitogen-activated protein kinases in the cardiovascular system Cardiovasc Res, March 1, 2000; 45(4): 826 - 842. [Abstract] [Full Text] [PDF]
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A. Nakano, C. P. Baines, S. O. Kim, S. L. Pelech, J. M. Downey, M. V. Cohen, and S. D. Critz Ischemic Preconditioning Activates MAPKAPK2 in the Isolated Rabbit Heart : Evidence for Involvement of p38 MAPK Circ. Res., February 4, 2000; 86(2): 144 - 151. [Abstract] [Full Text] [PDF]
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O. M. Hernandez, D. J. Discher, N. H. Bishopric, and K. A. Webster Rapid Activation of Neutral Sphingomyelinase by Hypoxia-Reoxygenation of Cardiac Myocytes Circ. Res., February 4, 2000; 86(2): 198 - 204. [Abstract] [Full Text] [PDF]
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G. Z. Feuerstein and P. R. Young Apoptosis in cardiac diseases: stress- and mitogen-activated signaling pathways Cardiovasc Res, February 1, 2000; 45(3): 560 - 569. [Abstract] [Full Text] [PDF]
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M. N. Sack, R. M. Smith, and L. H. Opie Tumor necrosis factor in myocardial hypertrophy and ischaemia -- an anti-apoptotic perspective Cardiovasc Res, February 1, 2000; 45(3): 688 - 695. [Full Text] [PDF]
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C. E. Ganote and S. C. Armstrong Adenosine and preconditioning in the rat heart Cardiovasc Res, January 1, 2000; 45(1): 134 - 140. [Full Text] [PDF]
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Y. Takeishi, J.-i. Abe, J.-D. Lee, H. Kawakatsu, R. A. Walsh, and B. C. Berk Differential Regulation of p90 Ribosomal S6 Kinase and Big Mitogen-Activated Protein Kinase 1 by Ischemia/Reperfusion and Oxidative Stress in Perfused Guinea Pig Hearts Circ. Res., December 3, 1999; 85(12): 1164 - 1172. [Abstract] [Full Text] [PDF]
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