Caspase-4 directly activates caspase-9 in endoplasmic reticulum stress-induced apoptosis in SH-SY5Y cells

The present study investigated the function of caspase-4 in endoplasmic reticulum (er) stress-induced apoptosis in human neuronal cell line sh-sy5y. tunicamycin,which is known to induce er stress,activated both caspase-9 and caspase-4,and the activation of caspase-4 preceded that of caspase-9. the caspase-4 inhibitor levd-cho suppressed both the apoptosis and caspase-9 activation. in addition,human recombinant active caspase-4 cleaved wild type and d330a mutant substituted asp-330 for alanine of human recombinant procaspase-9,but did not cleave d315a mutant substituted asp-315 for alanine. these results suggest that caspase-4 directly activates caspase-9 by the processing of procaspase-9 at asp-315 in er stress-induced neuronal apoptosis. © the japanese pharmacological society.