HCO(3)(-)-independent rescue from apoptosis by stilbene derivatives in rat cardiomyocytes |
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Authors: | Tanabe Shigeru Wang Xiaoming Takahashi Nobuyuki Uramoto Hiromi Okada Yasunobu |
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Institution: | Department of Cell Physiology and Molecular Physiology, National Institute for Physiological Sciences, Japan Science and Technology Agency, Myodaiji-cho, Okazaki 444-8585, Japan. |
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Abstract: | Apoptosis of rat cardiomyocytes induced by staurosporine is prevented by a stilbene derivative (DIDS), which is a known blocker of both Cl(-)/HCO(3)(-) exchangers and Cl(-) channels. To clarify its target, staurosporine-induced activation of caspase-3, DNA laddering and cell death were examined in cultured rat cardiomyocytes. Removal of ambient HCO(3)(-), which minimizes the function of Cl(-)/HCO(3)(-) exchangers, failed to affect the preventive effect of DIDS on apoptosis. A carboxylate analog Cl(-) channel blocker, which does not block Cl(-)/HCO(3)(-) exchangers, also inhibited apoptotic events. Thus, rescue by DIDS of cardiomyocytes from apoptosis is mediated by blockage of Cl(-) channels. |
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