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(Circulation. 1996;94:2185-2192.)
© 1996 American Heart Association, Inc.

Articles

Reperfusion Causes Significant Activation of Heat Shock Transcription Factor 1 in Ischemic Rat Heart

Junichiro Nishizawa, MD; Akira Nakai, MD, PhD; Toshio Higashi, MD, PhD; Masako Tanabe, MS; Shinichi Nomoto, MD, PhD; Katsuhiko Matsuda, MD, PhD; Toshihiko Ban, MD, PhD; Kazuhiro Nagata, PhD

the Department of Cardiovascular Surgery, Faculty of Medicine (J.N., S.N., K.M., T.B.), and Department of Cell Biology, Chest Disease Research Institute (J.N., A.N., T.H., M.T., K.N.), Kyoto University, Kyoto, Japan.

Correspondence to Kazuhiro Nagata, PhD, Department of Cell Biology, Chest Disease Research Institute, Kyoto University, Sakyo-ku, Kyoto 606-01, Japan. E-mail nagata@chest.chest.kyoto-u.ac.jp.

Background The myocardial protective role of heat shock protein (HSP) has been demonstrated, and there has been increasing interest in stress response in the heart. We examined the DNA-binding activity of heat shock transcription factor (HSF), by which the transcription of heat shock genes is mainly regulated, during heat shock or ischemia/reperfusion in isolated rat 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, which is present upstream of all heat shock genes. Induction of mRNAs for HSP70, HSP90, and GRP78 (glucose-regulated protein) was examined by Northern blot analysis. Although the activation of HSF during global ischemia was weak and rapidly attenuated, postischemic reperfusion induced a significant activation of HSF. In addition, although HSP70 mRNA was hardly induced during ischemia, its burst induction was detected during postischemic reperfusion. Supershift assays using specific antisera for HSF1 and HSF2 revealed that ischemia/reperfusion as well as heat shock induced the activation of HSF1 in hearts. Although the expression of HSP70 mRNA during heat shock was more vigorous than the expression during ischemia/reperfusion, the induction of HSP90 mRNA in postischemic reperfusion was significantly greater than that in heat shock.

Conclusions Our findings demonstrated that reperfusion causes a significant activation of HSF1 in ischemia-reperfused heart. The striking contrast between the induction of HSP70 mRNA and that of HSP90 mRNA suggests the presence of regulatory mechanisms other than HSF.

Key Words: heat shock factor • stress response • ischemia • reperfusion • myocardium

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