HCO(3)(-)-independent rescue from apoptosis by stilbene derivatives in rat cardiomyocytes.
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.
Tanabe
Shigeru
S
Department of Cell Physiology and Molecular Physiology, National Institute for Physiological Sciences, Japan Science and Technology Agency, Myodaiji-cho, Okazaki 444-8585, Japan.
Wang
Xiaoming
X
Takahashi
Nobuyuki
N
Uramoto
Hiromi
H
Okada
Yasunobu
Y
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology*; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001639:Bicarbonates / Q000378:metabolism*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D018118:Chloride Channels / Q000037:antagonists & inhibitors*; D053938:DNA Fragmentation / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects*; D009579:Nitrobenzoates / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D019311:Staurosporine / Q000494:pharmacology
D001639:Bicarbonates; D018118:Chloride Channels; D009579:Nitrobenzoates; D026902:Potassium Channel Blockers; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D019311:Staurosporine; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid