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

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)245-254
Number of pages10
JournalJournal of Cellular Biochemistry
Volume109
Issue number1
DOIs
Publication statusPublished - Jan 1 2010
Externally publishedYes

Keywords

  • BCL-2 family proteins
  • FAS
  • FASL
  • JNK
  • Phospholipase A

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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