期刊
JOURNAL OF PHARMACOLOGICAL SCIENCES
卷 115, 期 2, 页码 239-243出版社
JAPANESE PHARMACOLOGICAL SOC
DOI: 10.1254/jphs.10217SC
关键词
caspase-4; caspase-9; endoplasmic reticulum (ER) stress
资金
- [21590110]
- Grants-in-Aid for Scientific Research [21590110] Funding Source: KAKEN
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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