Taiwan cobra phospholipase A2-elicited JNK activation is responsible for autocrine Fas-mediated cell death and modulating Bcl-2 and Bax protein expression in human leukemia K562 cells

Ku Chung Chen, Wen Hsin Liu, Long Sen Chang

研究成果: 雜誌貢獻文章

10 引文 斯高帕斯(Scopus)

摘要

Phospholipase A2 (PLA2) from Naja naja atra venom induced apoptotic death of human leukemia K562 cells. Degradation of procaspases, production of tBid, loss of mitochondrial membrane potential, Bcl-2 degradation, mitochondrial translocation of Bax, and cytochrome c release were observed in PLA2-treated cells. Moreover, PLA2 treatment increased Fas and FasL protein expression. Upon exposure to PLA2, activation of p38 MAPK (mitogen-activated protein kinase) and JNK (c-Jun NH 2-terminal kinase) was found in K562 cells. SB202190 (p38 MAPK inhibitor) pretreatment enhanced cytotoxic effect of PLA2 and led to prolonged JNK activation, but failed to affect PLA2-induced upregulation of Fas and FasL protein expression. Sustained JNK activation aggravated caspase8/mitochondria-dependent death pathway, downregulated Bcl-2 expression and increased mitochondrial translocation of Bax. SP600125 (JNK inhibitor) abolished the cytotoxic effect of PLA2 and PLA 2-induced autocrine Fas death pathway. Transfection ASK1 siRNA and overexpression of dominant negative p38α MAPK proved that ASK1 pathway was responsible for PLA2-induced p38 MAPK and JNK activation and p38α MAPK activation suppressed dynamically persistent JNK activation. Downregulation of FADD abolished PLA2-induced procaspase-8 degradation and rescued viability of PLA2-treated cells. Taken together, our results indicate that JNK-mediated autocrine Fas/FasL apoptotic mechanism and modulation of Bcl-2 family proteins are involved in PLA 2-induced death of K562 cells.

原文英語
頁(從 - 到)245-254
頁數10
期刊Journal of Cellular Biochemistry
109
發行號1
DOIs
出版狀態已發佈 - 一月 1 2010
對外發佈Yes

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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