| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 Departments of Surgery and Physiology, University of Connecticut School of Medicine, Farmington, Connecticut 06030-1110; and 2 Department of Surgery, University of Colorado Health Sciences Center, Denver, Colorado 80262
Myocardial adaptation to ischemia has been shown to activate protein tyrosine kinase, potentiating activation of phospholipase D, which leads to the stimulation of mitogen-activated protein (MAP) kinases and MAP kinase-activated protein (MAPKAP) kinase 2. The present study sought to further examine the signal transduction pathway for the MAPKAP kinase 2 activation during ischemic adaptation. Isolated perfused rat hearts were adapted to ischemic stress by repeated ischemia and reperfusion. Hearts were pretreated with genistein to block tyrosine kinase, whereas SB-203580 was used to inhibit p38 MAP kinases. Western blot analysis demonstrated that p38 MAP kinase is phosphorylated during ischemic stress adaptation. Phosphorylation of p38 MAP kinase was blocked by genistein, suggesting that activation of p38 MAP kinase during ischemic adaptation is mediated by a tyrosine kinase signaling pathway. MAPKAP kinase 2 was estimated by following in vitro phosphorylation with recombinant human heat shock protein 27 as specific substrate for MAPKAP kinase 2. Again, both genistein and SB-203580 blocked the activation of MAPKAP kinase 2 during myocardial adaptation to ischemia. Immunofluorescence microscopy with anti-p38-antibody revealed that p38 MAP kinase is primarily localized in perinuclear regions. p38 MAP kinase moves to the nucleus after ischemic stress adaptation. After ischemia and reperfusion, cytoplasmic striations in the myocytes become obvious, indicating translocation of p38 MAP kinase from nucleus to cytoplasm. Corroborating these results, myocardial adaptation to ischemia improved the left ventricular functions and reduced myocardial infarction that were reversed by blocking either tyrosine kinase or p38 MAP kinase. These results demonstrate that myocardial adaptation to ischemia triggers a tyrosine kinase-regulated signaling pathway, leading to the translocation and activation of p38 MAP kinase and implicating a role for MAPKAP kinase 2.
ischemia-reperfusion; mitogen-activated protein kinases; p38 mitogen-activated protein kinase; mitogen-activated protein kinase-activated protein kinase 2; heat shock protein 27
This article has been cited by other articles:
|
|
 |
|
  C. Doucet, S. Milin, F. Favreau, T. Desurmont, E. Manguy, W. Hebrard, Y. Yamamoto, G. Mauco, M. Eugene, V. Papadopoulos, et al. A p38 mitogen-activated protein kinase inhibitor protects against renal damage in a non-heart-beating donor model Am J Physiol Renal Physiol, July 1, 2008; 295(1): F179 - F191. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. T. Lee, M. Kim, J. H. Song, S. W. C. Chen, G. Gubitosa, and C. W. Emala Sevoflurane-mediated TGF-{beta}1 signaling in renal proximal tubule cells Am J Physiol Renal Physiol, February 1, 2008; 294(2): F371 - F378. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Lekli, G. Szabo, B. Juhasz, S. Das, M. Das, E. Varga, L. Szendrei, R. Gesztelyi, J. Varadi, I. Bak, et al. Protective mechanisms of resveratrol against ischemia-reperfusion-induced damage in hearts obtained from Zucker obese rats: the role of GLUT-4 and endothelin Am J Physiol Heart Circ Physiol, February 1, 2008; 294(2): H859 - H866. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Li, J. Y. Ma, I. Kerr, S. Chakravarty, S. Dugar, G. Schreiner, and A. A. Protter Selective inhibition of p38{alpha} MAPK improves cardiac function and reduces myocardial apoptosis in rat model of myocardial injury Am J Physiol Heart Circ Physiol, October 1, 2006; 291(4): H1972 - H1977. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. T. Lee, M. Kim, M. Jan, and C. W. Emala Anti-inflammatory and antinecrotic effects of the volatile anesthetic sevoflurane in kidney proximal tubule cells Am J Physiol Renal Physiol, July 1, 2006; 291(1): F67 - F78. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Maulik Effect of p38 MAP kinase on cellular events during ischemia and reperfusion: possible therapy Am J Physiol Heart Circ Physiol, December 1, 2005; 289(6): H2302 - H2303. [Full Text] [PDF]
|
|
|
|
|
|
S. L. House, K. Branch, G. Newman, T. Doetschman, and J. E. J. Schultz Cardioprotection induced by cardiac-specific overexpression of fibroblast growth factor-2 is mediated by the MAPK cascade Am J Physiol Heart Circ Physiol, November 1, 2005; 289(5): H2167 - H2175. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Ballard-Croft, G. Kristo, Y. Yoshimura, E. Reid, B. J. Keith, R. M. Mentzer Jr., and R. D. Lasley Acute adenosine preconditioning is mediated by p38 MAPK activation in discrete subcellular compartments Am J Physiol Heart Circ Physiol, March 1, 2005; 288(3): H1359 - H1366. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Chen, R. Rajashree, Q. Liu, and P. Hofmann Acute p38 MAPK activation decreases force development in ventricular myocytes Am J Physiol Heart Circ Physiol, December 1, 2003; 285(6): H2578 - H2586. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. YELLON and J. M. DOWNEY Preconditioning the Myocardium: From Cellular Physiology to Clinical Cardiology Physiol Rev, October 1, 2003; 83(4): 1113 - 1151. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-L. Tang, E. Kodani, H. Takano, M. Hill, K. Shinmura, T. M. Vondriska, P. Ping, and R. Bolli Protein tyrosine kinase signaling is necessary for NO donor-induced late preconditioning against myocardial stunning Am J Physiol Heart Circ Physiol, April 1, 2003; 284(4): H1441 - H1448. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Qin, J. M. Downey, and M. V. Cohen Acetylcholine but not adenosine triggers preconditioning through PI3-kinase and a tyrosine kinase Am J Physiol Heart Circ Physiol, February 1, 2003; 284(2): H727 - H734. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Krieg, Q. Qin, E. C. McIntosh, M. V. Cohen, and J. M. Downey ACh and adenosine activate PI3-kinase in rabbit hearts through transactivation of receptor tyrosine kinases Am J Physiol Heart Circ Physiol, December 1, 2002; 283(6): H2322 - H2330. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Dawn, H. Takano, X.-L. Tang, E. Kodani, S. Banerjee, A. Rezazadeh, Y. Qiu, and R. Bolli Role of Src protein tyrosine kinases in late preconditioning against myocardial infarction Am J Physiol Heart Circ Physiol, August 1, 2002; 283(2): H549 - H556. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Ohnuma, T. Miura, T. Miki, M. Tanno, A. Kuno, A. Tsuchida, and K. Shimamoto Opening of mitochondrial KATP channel occurs downstream of PKC-epsilon activation in the mechanism of preconditioning Am J Physiol Heart Circ Physiol, July 1, 2002; 283(1): H440 - H447. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Schulz, M. V Cohen, M. Behrends, J. M Downey, and G. Heusch Signal transduction of ischemic preconditioning Cardiovasc Res, November 1, 2001; 52(2): 181 - 198. [Full Text] [PDF]
|
|
|
|
|
|
J. An, S. G. Varadarajan, E. Novalija, and D. F. Stowe Ischemic and anesthetic preconditioning reduces cytosolic [Ca2+] and improves Ca2+ responses in intact hearts Am J Physiol Heart Circ Physiol, October 1, 2001; 281(4): H1508 - H1523. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Hattori, H. Otani, T. Uchiyama, H. Imamura, J. Cui, N. Maulik, G. A. Cordis, L. Zhu, and D. K. Das Src tyrosine kinase is the trigger but not the mediator of ischemic preconditioning Am J Physiol Heart Circ Physiol, September 1, 2001; 281(3): H1066 - H1074. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Yue, M. Krenz, M. V. Cohen, J. M. Downey, and S. D. Critz Menadione mimics the infarct-limiting effect of preconditioning in isolated rat hearts Am J Physiol Heart Circ Physiol, August 1, 2001; 281(2): H590 - H595. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 P. S. RAY, J. L. MARTIN, E. A. SWANSON, H. OTANI, W. H. DILLMANN, and D. K. DAS Transgene overexpression of {alpha}B crystallin confers simultaneous protection against cardiomyocyte apoptosis and necrosis during myocardial ischemia and reperfusion FASEB J, February 1, 2001; 15(2): 393 - 402. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Xu, Y. Wang, K. Hirai, A. Ayub, and M. Ashraf Calcium preconditioning inhibits mitochondrial permeability transition and apoptosis Am J Physiol Heart Circ Physiol, February 1, 2001; 280(2): H899 - H908. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 M. Kitakaze, K. Node, H. Asanuma, S. Takashima, Y. Sakata, M. Asakura, S. Sanada, Y. Shinozaki, H. Mori, T. Kuzuya, et al. Protein Tyrosine Kinase Is Not Involved in the Infarct Size-Limiting Effect of Ischemic Preconditioning in Canine Hearts Circ. Res., August 18, 2000; 87(4): 303 - 308. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
P. Ping and E. Murphy Role of p38 Mitogen-Activated Protein Kinases in Preconditioning : A Detrimental Factor or a Protective Kinase? Circ. Res., May 12, 2000; 86(9): 921 - 922. [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
R. M. Fryer, J. T. Eells, A. K. Hsu, M. M. Henry, and G. J. Gross Ischemic preconditioning in rats: role of mitochondrial KATP channel in preservation of mitochondrial function Am J Physiol Heart Circ Physiol, January 1, 2000; 278(1): H305 - H312. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. M. Vondriska, J. Zhang, C. Song, X.-L. Tang, X. Cao, C. P. Baines, J. M. Pass, S. Wang, R. Bolli, and P. Ping Protein Kinase C {epsilon}-Src Modules Direct Signal Transduction in Nitric Oxide-Induced Cardioprotection : Complex Formation as a Means for Cardioprotective Signaling Circ. Res., June 22, 2001; 88(12): 1306 - 1313. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
