Nanosecond pulsed electric fields (nsPEFs) activate intrinsic caspase-dependent and caspase-independent cell death in Jurkat cells

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• 作者：Wei Ren¹ ; Nova M. Sain ; Stephen J. Beebe ; ^{sbeebe@odu.edu}
• 关键词：nsPEFs ; nanosecond pulsed electric fields ; 螖C-8 ; caspase-8 deficient Jurkat clone ; 螖APAF-1 ; APAF-1 deficient Jurkat clone ; APAF-1 ; apoptotic protease activating factor 1 ; FADD ; fas-associated protein with death domain ; DISC ; death-induced signaling comp
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2012
• 期刊代码：159_0006291x
• 类别：bio
• 出版时间：18 May, 2012
• 卷：421
• 期：4
• 页码：808-812
• 文件大小：317 K

摘要

NsPEF ablation induces apoptosis markers, but specific cell death pathways have not been fully defined. To identify nsPEF-activated cell death pathways, wildtype human Jurkat cells and clones with deficiencies in extrinsic and intrinsic apoptosis pathways were investigated. NsPEFs activated caspase isozymes and induced identical electric field-dependent cell death in clones deficient in FADD or caspase-8, indicating that extrinsic apoptosis pathways were not activated. This was confirmed when cytochrome c release was shown to be unaffected by the pan caspase inhibitor, z-VAD-fmk. NsPEF-treated APAF-1-silenced cells did not exhibit caspase-3/7 and -9 activities and corresponding electric field-dependent cell death in this clone was attenuated compared to its vector control at low, but not at high electric fields. These data demonstrate that nsPEFs induce intrinsic apoptosis activate by cytochrome c release from mitochondria through an APAF-1- and caspase-dependent pathway as well as through caspase-independent mechanisms that remain to be defined. Furthermore, the results establish that nsPEFs can overcome natural and oncogenic mechanisms that promote cell survival through inhibition of apoptosis and other cell death mechanisms.