Sequential caspase-2 and caspase-8 activation upstream of mitochondria during ceramideand etoposide-induced apoptosis.

doi:10.1074/jbc.M404726200

中山醫學大學機構典藏 CSMUIR > 醫學院 > 免疫學研究所 > 期刊論文 > Item 310902500/11785

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/11785

Title:	Sequential caspase-2 and caspase-8 activation upstream of mitochondria during ceramideand etoposide-induced apoptosis.
Authors:	Lin, CF Chen, CL Chang, WT Jan, MS Hsu, LJ Wu, RH Tang, MJ Chang, WC Lin, YS
Contributors:	中山醫學大學
Date:	2004
Issue Date:	2015-07-29T04:45:49Z (UTC)
ISSN:	0021-9258
Abstract:	Recently, caspase-2 was shown to act upstream of mitochondria in stress-induced apoptosis. Activation of caspase-8, a key event in death receptor-mediated apoptosis, also has been demonstrated in death receptor-independent apoptosis. The regulation of these initiator caspases, which trigger the mitochondrial apoptotic pathway, is unclear. Here we report a potential regulatory role of caspase-2 on caspase-8 during ceramide-induced apoptosis. Our results demonstrate the sequential events of initiator caspase-2 and caspase-8 activation, Bid cleavage and translocation, and mitochondrial damage followed by downstream caspase-9 and -3 activation and cell apoptosis after ceramide induction in T cell lines. The expression of truncated Bid (tBid) and the reduction in mitochondrial transmembrane potential were blocked by caspase-2 or caspase-8, but not caspase-3, knockdown using an RNA interference technique. Ceramide-induced caspase-8 activation, mitochondrial damage, and apoptosis were blocked in caspase-2 short interfering RNA-expressing cells. Therefore, caspase-2 acts upstream of caspase-8 during ceramide-induced mitochondrial apoptosis. Similarly, sequential caspase-2 and caspase-8 activation upstream of mitochondria was also observed in etoposide-induced apoptosis. These data suggest sequential initiator caspase-2 and caspase-8 activation in the mitochondrial apoptotic pathway induced by ceramide or etoposide. Copyright 2004 American Society for Biochemistry and Molecular Biology, Inc.
URI:	https://ir.csmu.edu.tw:8080/ir/handle/310902500/11785 http://dx.doi.org/10.1074/jbc.M404726200
Relation:	J Biol Chem. 2004 Sep 24;279(39):40755-61.
Appears in Collections:	[免疫學研究所] 期刊論文

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