© 2000 by European Society of Cardiology
Copyright © 2000, European Society of Cardiology
Activation of JAK/STAT pathway transduces cytoprotective signal in rat acute myocardial infarction
Department of Molecular Medicine, Osaka University Medical School, Suita, Osaka 565-0871, Japan
* Corresponding author. Tel.: +81-6-6879-3835; fax: +81-6-6879-3839 takihara{at}imed3.med.osaka-u.ac.jp
Objectives: We reported that the activation of gp130 transduced hypertrophic and cytoprotective signals via Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway in cardiac myocytes. Recent in vivo experiments have demonstrated that the JAK/STAT pathway is activated in acute pressure overload hearts. The present study was designed to examine whether the JAK/STAT pathway is also activated in acute myocardial infarction (AMI) and to determine its pathophysiological roles in ischemic heart disease. Methods and results: AMI model was generated by the ligation of proximal left anterior descending coronary artery of male Wistar rat. They were sacrificed at various time points ranging from 1 to 24 h after coronary ligation and their hearts were examined. Tyrosine phosphorylation of STAT3 was observed in the myocardium obtained from both the ischemic area and the healthy border area adjacent to the infarcted area. The AMI rats were next randomly assigned to two groups, one with coronary ligation only (group M), and the other with coronary ligation with AG-490 treatment (1 mg/kg i.v., every 4 h), a specific JAK2 inhibitor (group A). In group A, phosphorylation of STAT3 was significantly suppressed and caspase-3 activity and Bax expression were significantly increased in the myocardium after AMI. In group M, few apoptotic myocytes were identified in the border area by means of TUNEL assay. However, a significant increase in apoptotic cells was observed in group A. Conclusions: Administration of JAK2 inhibitor resulted in deterioration of myocardial viability in AMI hearts. The JAK/STAT pathway is activated in AMI myocardium and plays a pivotal role in cytoprotective signaling.
KEYWORDS Apoptosis; Cytokines; Infarction; Signal transduction
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Kurdi and G. W. Booz JAK redux: a second look at the regulation and role of JAKs in the heart Am J Physiol Heart Circ Physiol, November 1, 2009; 297(5): H1545 - H1556. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Frias, U. Lang, C. Gerber-Wicht, and R. W. James Native and reconstituted HDL protect cardiomyocytes from doxorubicin-induced apoptosis Cardiovasc Res, September 18, 2009; (2009) cvp289v2. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Pautz, P. Rauschkolb, N. Schmidt, J. Art, M. Oelze, P. Wenzel, U. Forstermann, A. Daiber, and H. Kleinert Effects of nitroglycerin or pentaerithrityl tetranitrate treatment on the gene expression in rat hearts: evidence for cardiotoxic and cardioprotective effects Physiol Genomics, July 9, 2009; 38(2): 176 - 185. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Frias, R. W. James, C. Gerber-Wicht, and U. Lang Native and reconstituted HDL activate Stat3 in ventricular cardiomyocytes via ERK1/2: Role of sphingosine-1-phosphate Cardiovasc Res, May 1, 2009; 82(2): 313 - 323. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Frias, S. Somers, C. Gerber-Wicht, L. H. Opie, S. Lecour, and U. Lang The PGE2-Stat3 interaction in doxorubicin-induced myocardial apoptosis Cardiovasc Res, October 1, 2008; 80(1): 69 - 77. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D Mocini, P Muso, E Guendouz, L De Marco, L Mele, R Cini, P Sordini, A Alois, A Costantino, S Arima, et al. Endogenous erythropoietin and a single bolus of 40,000 IU of epoetin alpha do not protect the heart from ischaemia-reperfusion injury during extracorporeal circulation for cardiac surgery Perfusion, May 1, 2008; 23(3): 187 - 192. [Abstract] [PDF]
|
|
|
|
 |
|
 J. F. Giani, M. M. Gironacci, M. C. Munoz, D. Turyn, and F. P. Dominici Angiotensin-(1-7) has a dual role on growth-promoting signalling pathways in rat heart in vivo by stimulating STAT3 and STAT5a/b phosphorylation and inhibiting angiotensin II-stimulated ERK1/2 and Rho kinase activity Exp Physiol, May 1, 2008; 93(5): 570 - 578. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. C. Huffman, S. E. Koch, and K. L. Butler Coronary effluent from a preconditioned heart activates the JAK-STAT pathway and induces cardioprotection in a donor heart Am J Physiol Heart Circ Physiol, January 1, 2008; 294(1): H257 - H262. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. K. Sze, D. P. V. de Kleijn, R. C. Lai, E. Khia Way Tan, H. Zhao, K. S. Yeo, T. Y. Low, Q. Lian, C. N. Lee, W. Mitchell, et al. Elucidating the Secretion Proteome of Human Embryonic Stem Cell-derived Mesenchymal Stem Cells Mol. Cell. Proteomics, October 1, 2007; 6(10): 1680 - 1689. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Wang, W. Zhang, P. Crisostomo, T. Markel, K. K. Meldrum, X. Y. Fu, and D. R. Meldrum Endothelial STAT3 plays a critical role in generalized myocardial proinflammatory and proapoptotic signaling Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2101 - H2108. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Wang, W. Zhang, P. Crisostomo, T. Markel, K. K. Meldrum, X. Y. Fu, and D. R. Meldrum Sex differences in endothelial STAT3 mediate sex differences in myocardial inflammation Am J Physiol Endocrinol Metab, September 1, 2007; 293(3): E872 - E877. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Dziennis, T. Jia, O. K. Ronnekleiv, P. D. Hurn, and N. J. Alkayed Role of Signal Transducer and Activator of Transcription-3 in Estradiol-Mediated Neuroprotection J. Neurosci., July 4, 2007; 27(27): 7268 - 7274. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Frias, M. C. Rebsamen, C. Gerber-Wicht, and U. Lang Prostaglandin E2 activates Stat3 in neonatal rat ventricular cardiomyocytes: A role in cardiac hypertrophy Cardiovasc Res, January 1, 2007; 73(1): 57 - 65. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Hilfiker-Kleiner, U. Landmesser, and H. Drexler Molecular Mechanisms in Heart Failure: Focus on Cardiac Hypertrophy, Inflammation, Angiogenesis, and Apoptosis J. Am. Coll. Cardiol., October 27, 2006; 48(9_Suppl_A): A56 - A66. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Morimoto, M. Takahashi, A. Izawa, H. Ise, M. Hongo, P. E. Kolattukudy, and U. Ikeda Cardiac Overexpression of Monocyte Chemoattractant Protein-1 in Transgenic Mice Prevents Cardiac Dysfunction and Remodeling After Myocardial Infarction Circ. Res., October 13, 2006; 99(8): 891 - 899. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Zhang, P. Shan, G. Jiang, S. S-M. Zhang, L. E. Otterbein, X.-Y. Fu, and P. J. Lee Endothelial STAT3 is essential for the protective effects of HO-1 in oxidant-induced lung injury FASEB J, October 1, 2006; 20(12): 2156 - 2158. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. R. Gross, A. K. Hsu, and G. J. Gross The JAK/STAT pathway is essential for opioid-induced cardioprotection: JAK2 as a mediator of STAT3, Akt, and GSK-3beta Am J Physiol Heart Circ Physiol, August 1, 2006; 291(2): H827 - H834. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. L. Butler, L. C. Huffman, S. E. Koch, H. S. Hahn, and J. K. Gwathmey STAT-3 activation is necessary for ischemic preconditioning in hypertrophied myocardium Am J Physiol Heart Circ Physiol, August 1, 2006; 291(2): H797 - H803. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Tada, Y. Kagaya, M. Takeda, J. Ohta, Y. Asaumi, K. Satoh, K. Ito, A. Karibe, K. Shirato, N. Minegishi, et al. Endogenous erythropoietin system in non-hematopoietic lineage cells plays a protective role in myocardial ischemia/reperfusion Cardiovasc Res, August 1, 2006; 71(3): 466 - 477. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Yano, R. Ozono, Y. Oishi, M. Kambe, M. Yoshizumi, T. Ishida, S. Omura, T. Oshima, and K. Igarashi Genetic ablation of the transcription repressor Bach1 leads to myocardial protection against ischemia/reperfusion in mice. Genes Cells, July 1, 2006; 11(7): 791 - 803. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Colombo, S. Gatti, F. Turcatti, A. Sordi, L. R. Fassati, F. Bonino, J. M. Lipton, and A. Catania Gene Expression Profiling Reveals Multiple Protective Influences of the Peptide {alpha}-Melanocyte-Stimulating Hormone in Experimental Heart Transplantation J. Immunol., September 1, 2005; 175(5): 3391 - 3401. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. P. Yang, K. Irani, S. Mattagajasingh, A. DiPaula, F. Khanday, M. Ozaki, K. Fox-Talbot, W. M. Baldwin III, and L. C. Becker Signal Transducer and Activator of Transcription 3{alpha} and Specificity Protein 1 Interact to Upregulate Intercellular Adhesion Molecule-1 in Ischemic-Reperfused Myocardium and Vascular Endothelium Arterioscler Thromb Vasc Biol, July 1, 2005; 25(7): 1395 - 1400. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Smith, N. Suleman, L. Lacerda, L. H. Opie, S. Akira, K. R. Chien, and M. N. Sack Genetic depletion of cardiac myocyte STAT-3 abolishes classical preconditioning Cardiovasc Res, September 1, 2004; 63(4): 611 - 616. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Hilfiker-Kleiner, A. Hilfiker, M. Fuchs, K. Kaminski, A. Schaefer, B. Schieffer, A. Hillmer, A. Schmiedl, Z. Ding, E. Podewski, et al. Signal Transducer and Activator of Transcription 3 Is Required for Myocardial Capillary Growth, Control of Interstitial Matrix Deposition, and Heart Protection From Ischemic Injury Circ. Res., July 23, 2004; 95(2): 187 - 195. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. Jacoby, A. Kalinowski, M.-G. Liu, S. S.-M. Zhang, Q. Gao, G.-X. Chai, L. Ji, Y. Iwamoto, E. Li, M. Schneider, et al. Cardiomyocyte-restricted knockout of STAT3 results in higher sensitivity to inflammation, cardiac fibrosis, and heart failure with advanced age PNAS, October 28, 2003; 100(22): 12929 - 12934. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Yin, P. Li, M. Zheng, L. Chen, Q. Xu, K. Chen, Y.-y. Wang, Y.-y. Zhang, and C. Han Interleukin-6 Family of Cytokines Mediates Isoproterenol-induced Delayed STAT3 Activation in Mouse Heart J. Biol. Chem., May 30, 2003; 278(23): 21070 - 21075. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Ogata, M. Takahashi, S. Ueno, K. Takeuchi, T. Okada, H. Mano, S. Ookawara, K. Ozawa, B. C. Berk, U. Ikeda, et al. Antiapoptotic Effect of Endothelin-1 in Rat Cardiomyocytes In Vitro Hypertension, May 1, 2003; 41(5): 1156 - 1163. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Yu, R. H. Kennedy, and S. J. Liu JAK2/STAT3, Not ERK1/2, Mediates Interleukin-6-induced Activation of Inducible Nitric-oxide Synthase and Decrease in Contractility of Adult Ventricular Myocytes J. Biol. Chem., April 25, 2003; 278(18): 16304 - 16309. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. El-Adawi, L. Deng, A. Tramontano, S. Smith, E. Mascareno, K. Ganguly, R. Castillo, and N. El-Sherif The functional role of the JAK-STAT pathway in post-infarction remodeling Cardiovasc Res, January 1, 2003; 57(1): 129 - 138. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Fuchs and H. Drexler Pharmacotherapy of chronic heart failure: current status and future aspects Eur. Heart J. Suppl., December 1, 2002; 4(suppl_I): I81 - I87. [Abstract] [PDF]
|
|
|
|
|
|
S. Shaw, M. Bencherif, and M. B. Marrero Janus Kinase 2, an Early Target of alpha 7 Nicotinic Acetylcholine Receptor-mediated Neuroprotection against Abeta -(1-42) Amyloid J. Biol. Chem., November 15, 2002; 277(47): 44920 - 44924. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P A J Krijnen, R Nijmeijer, C J L M Meijer, C A Visser, C E Hack, and H W M Niessen Apoptosis in myocardial ischaemia and infarction J. Clin. Pathol., November 1, 2002; 55(11): 801 - 811. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-T. Xuan, Y. Guo, H. Han, Y. Zhu, and R. Bolli An essential role of the JAK-STAT pathway in ischemic preconditioning PNAS, July 31, 2001; 98(16): 9050 - 9055. [Abstract] [Full Text] [PDF]
|
|