This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nishizawa, J. Articles by Nagata, K. Search for Related Content PubMed PubMed Citation Articles by Nishizawa, J. Articles by Nagata, K. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB ALLOPURINOL Medline Plus Health Information Cardiomyopathy Related Collections Animal models of human disease Ischemic biology - basic studies

(Circulation. 1999;99:934-941.)
© 1999 American Heart Association, Inc.

Basic Science Reports

Reactive Oxygen Species Play an Important Role in the Activation of Heat Shock Factor 1 in Ischemic-Reperfused Heart

Presented in part at the 70th Scientific Sessions of the American Heart Association, Orlando, Fla, November 9–12, 1997, and published in abstract form (Circulation. 1997;96[suppl I]:I-312).

Junichiro Nishizawa, MD, PhD; Akira Nakai, MD, PhD; Katsuhiko Matsuda, MD, PhD; Masashi Komeda, MD, PhD; Toshihiko Ban, MD, PhD; Kazuhiro Nagata, PhD

From the Department of Cardiovascular Surgery, Faculty of Medicine (J.N., K.M., M.K., T.B.), and the Department of Molecular and Cellular Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto (J.N., A.N., K.N.); and Core Research for Evolutional Science and Technology, Japanese Science and Technology Cooperation, Kawaguchi (A.N., K.N.), Japan.

Correspondence to Kazuhiro Nagata, PhD, Department of Molecular and Cellular Biology, Institute for Frontier Medical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8397, Japan. E-mail nagata{at}chest.chest.kyoto-u.ac.jp

Background—The myocardial protective role of heat shock protein (HSP) has been demonstrated. Recently, we reported that ischemia/reperfusion induced a significant activation of heat shock factor (HSF) 1 and an accumulation of mRNA for HSP70 and HSP90. We examined the role of reactive oxygen species (ROSs) in the induction of stress response in the ischemic-reperfused heart.

Methods and Results—Rat hearts were isolated and perfused with Krebs-Henseleit buffer by the Langendorff method. Whole-cell extracts were prepared for gel mobility shift assay using oligonucleotides containing the heat shock element. Induction of mRNA for HSP70 and HSP90 was examined by Northern blot analysis. Repetitive ischemia/reperfusion, which causes recurrent bursts of free radical generation, resulted in burst activation of HSF1, and this burst activation was significantly reduced with either allopurinol 1 mmol/L (an inhibitor of xanthine oxidase) or catalase 2x10⁵ U/L (a scavenger of H₂O₂). Significant activation of HSF1 was observed on perfusion with buffer containing H₂O₂ 150 µmol/L or xanthine 1 mmol/L plus xanthine oxidase 5 U/L. The accumulation of mRNA for HSP70 or HSP90 after repetitive ischemia/reperfusion was reduced with either allopurinol or catalase.

Conclusions—Our findings demonstrate that ROSs play an important role in the activation of HSF1 and the accumulation of mRNA for HSP70 and HSP90 in the ischemic-reperfused heart.

Key Words: heat shock factor • reactive oxygen species • myocardium • ischemia • reperfusion

This article has been cited by other articles:

				R. Mangat, T. Singal, N. S. Dhalla, and P. S. Tappia Inhibition of phospholipase C-{gamma}1 augments the decrease in cardiomyocyte viability by H2O2 Am J Physiol Heart Circ Physiol, August 1, 2006; 291(2): H854 - H860. [Abstract] [Full Text] [PDF]

				P. Pacher, A. Nivorozhkin, and C. Szabo Therapeutic effects of xanthine oxidase inhibitors: renaissance half a century after the discovery of allopurinol. Pharmacol. Rev., March 1, 2006; 58(1): 87 - 114. [Abstract] [Full Text] [PDF]

				J. Wang, H. He, L. Yu, H. H.-x. Xia, M. C. M. Lin, Q. Gu, M. Li, B. Zou, X. An, B. Jiang, et al. HSF1 Down-regulates XAF1 through Transcriptional Regulation J. Biol. Chem., February 3, 2006; 281(5): 2451 - 2459. [Abstract] [Full Text] [PDF]

				M. Frederich, L. Zhang, and J. A. Balschi Hypoxia and AMP independently regulate AMP-activated protein kinase activity in heart Am J Physiol Heart Circ Physiol, May 1, 2005; 288(5): H2412 - H2421. [Abstract] [Full Text] [PDF]

				N. C Chi and J. S Karliner Molecular determinants of responses to myocardial ischemia/reperfusion injury: focus on hypoxia-inducible and heat shock factors Cardiovasc Res, February 15, 2004; 61(3): 437 - 447. [Abstract] [Full Text] [PDF]

				H. V. CAREY, M. T. ANDREWS, and S. L. MARTIN Mammalian Hibernation: Cellular and Molecular Responses to Depressed Metabolism and Low Temperature Physiol Rev, October 1, 2003; 83(4): 1153 - 1181. [Abstract] [Full Text] [PDF]

				C. Depre, L. Wang, J. E. Tomlinson, V. Gaussin, M. Abdellatif, J. N. Topper, and S. F. Vatner Characterization of pDJA1, a cardiac-specific chaperone found by genomic profiling of the post-ischemic swine heart Cardiovasc Res, April 1, 2003; 58(1): 126 - 135. [Abstract] [Full Text] [PDF]

				P. Sancho, A. Troyano, C. Fernandez, E. De Blas, and P. Aller Differential Effects of Catalase on Apoptosis Induction in Human Promonocytic Cells. Relationships with Heat-Shock Protein Expression Mol. Pharmacol., March 1, 2003; 63(3): 581 - 589. [Abstract] [Full Text] [PDF]

				J. Nishizawa, A. Nakai, M. Komeda, T. Ban, and K. Nagata Increased preload directly induces the activation of heat shock transcription factor 1 in the left ventricular overloaded heart Cardiovasc Res, August 1, 2002; 55(2): 341 - 348. [Abstract] [Full Text] [PDF]

				I. J. Benjamin and E. Christians Exercise, Estrogen, and Ischemic Cardioprotection by Heat Shock Protein 70 Circ. Res., May 3, 2002; 90(8): 833 - 835. [Full Text] [PDF]

				L. H. E. H. Snoeckx, R. N. Cornelussen, F. A. Van Nieuwenhoven, R. S. Reneman, and G. J. Van der Vusse Heat Shock Proteins and Cardiovascular Pathophysiology Physiol Rev, October 1, 2001; 81(4): 1461 - 1497. [Abstract] [Full Text] [PDF]

				D. S Latchman Heat shock proteins and cardiac protection Cardiovasc Res, September 1, 2001; 51(4): 637 - 646. [Abstract] [Full Text] [PDF]

				N. R. Madamanchi, S. Li, C. Patterson, and M. S. Runge Reactive Oxygen Species Regulate Heat-Shock Protein 70 via the JAK/STAT Pathway Arterioscler. Thromb. Vasc. Biol., March 1, 2001; 21(3): 321 - 326. [Abstract] [Full Text] [PDF]

				H. H. Patel, A. Hsu, and G. J. Gross Cardioprotection is strain dependent in rat in response to whole body hyperthermia Am J Physiol Heart Circ Physiol, March 1, 2001; 280(3): H1208 - H1214. [Abstract] [Full Text] [PDF]

				W. E. Johnston Preconditioning the Brain and Heart: Implications for Cardiac Surgery Seminars in Cardiothoracic and Vascular Anesthesia, July 1, 2000; 4(2): 70 - 79. [Abstract] [PDF]

				N. R. Madamanchi, S. Li, C. Patterson, and M. S. Runge Thrombin Regulates Vascular Smooth Muscle Cell Growth and Heat Shock Proteins via the JAK-STAT Pathway J. Biol. Chem., May 25, 2001; 276(22): 18915 - 18924. [Abstract] [Full Text] [PDF]