Journal of Pharmacological Sciences
Online ISSN : 1347-8648
Print ISSN : 1347-8613
ISSN-L : 1347-8613
Short Communications
Caspase-4 Directly Activates Caspase-9 in Endoplasmic Reticulum Stress–Induced Apoptosis in SH-SY5Y Cells
Akiko YamamuroTakashi KishinoYu OhshimaYasuhiro YoshiokaTomoki KimuraAtsushi KasaiSadaaki Maeda
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2011 Volume 115 Issue 2 Pages 239-243

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Abstract

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.

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© The Japanese Pharmacological Society 2011
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