Hsp70 attenuates hypoxia/reoxygenation-induced activation of poly(ADP-ribose) synthetase in the nucleus of adult rat cardiomyocytes |
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Authors: | Tanonaka Kouichi Toga Wakako Takahashi Masaya Kawana Ken-ichiro Miyamoto Yuki Yoshida Hiroyuki Takeo Satoshi |
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Affiliation: | (1) Department of Pharmacology, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan |
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Abstract: | Effects of heat shock protein 70 (Hsp70) translocated to nuclear fraction on hypoxia/reoxygenation injury was examined by using adult cardiomyocytes isolated from rats. Cardiomyocytes were exposed to heat shock at 42°C for 15 min (HS group), and then incubated at 37°C for 6–24 h. Hsp70 production increased and the protein translocated from cytosol to nucleus. The maximum level of Hsp70 in the nuclear fraction was observed 12 h after HS. When cardiomyocytes without exposure to HS (nHS group) were subjected to 120 min hypoxia/15 min reoxygenation (Hypo/Reoxy), post-hypoxic cell viability was approximately 25% of the pre-hypoxic value. A rise in poly(ADP-ribose) synthetase (PARS) activity in the nuclear fraction was observed in nHS group, associated with an increase in polyADP-ribosylated protein. In contrast, post-hypoxic cell viability of HS group was approximately 60% of the pre-hypoxic value. Hypo/reoxy-induced rise in PARS activity and increase in polyADP-ribosylated protein were attenuated in HS group. To confirm the relationship between an increase in cell viability after Hypo/Reoxy and attenuation of PARS activation, cardiomyocytes without exposure to HS were subjected to Hypo/Reoxy in the presence of 1 mM 3-aminobenzamide, an inhibitor of PARS. Treatment of cells with 3-aminobenzamide attenuated Hypo/Reoxy-induced decrease in cell viability. These results suggest that Hsp70 translocated into nucleus after HS may attenuate PARS activation during Hypo/Reoxy, leading to the cytoprotection of cardiomyocytes against Hypo/Reoxy injury. |
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Keywords: | cardiomyocyte cytoprotection Hsp70 hypoxia/reoxygenation injury nucleus poly(ADP-ribose) synthetase translocation |
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