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(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

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