Differential roles for Bak in Triton X-100- and deoxycholate-induced apoptosis.
We recently reported that Bax activation occurs downstream of caspase activation in Triton X-100 (TX)-induced apoptosis. Here, Bak was found to be activated in TX-induced apoptosis. Although z-VAD-fmk completely suppressed Bax activation, it only partially attenuated TX-induced Bak activation. Moreover, activation of both Bak and Bax was detected in apoptosis induced by deoxycholate, a physiological detergent in bile. z-VAD-fmk completely suppressed deoxycholate-induced Bak as well as Bax activation. Furthermore, Bak siRNA attenuated TX- but not deoxycholate-induced caspase activation. These results suggest that Bak activation may occur upstream of caspase activation in TX- but not deoxycholate-induced apoptosis and that the mechanism of TX-induced apoptosis may differ from that of deoxycholate-induced apoptosis at least with regard to the role for Bak.
Sawai
Hirofumi
H
Department of Internal Medicine, Osaka Dental University, 8-1 Kuzuhahanazonocho, Hirakata, Osaka 573-1121, Japan.
Domae
Naochika
N
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017209:Apoptosis; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D003840:Deoxycholic Acid / Q000633:toxicity*; D006801:Humans; D017830:Octoxynol / Q000633:toxicity*; D034741:RNA, Small Interfering / Q000235:genetics; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000235:genetics / Q000378:metabolism*
D000590:Amino Acid Chloromethyl Ketones; C494772:BAK1 protein, human; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D034741:RNA, Small Interfering; D050998:bcl-2 Homologous Antagonist-Killer Protein; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D003840:Deoxycholic Acid; D017830:Octoxynol; D020169:Caspases