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Taiwan cobra phospholipase A 2 ‐elicited JNK activation is responsible for autocrine fas‐mediated cell death and modulating Bcl‐2 and Bax protein expression in human leukemia K562 cells
Author(s) -
Chen KuChung,
Liu WenHsin,
Chang LongSen
Publication year - 2009
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.22404
Subject(s) - fas ligand , k562 cells , p38 mitogen activated protein kinases , autocrine signalling , mapk/erk pathway , microbiology and biotechnology , fadd , apoptosis , programmed cell death , biology , protein kinase a , kinase , chemistry , cell culture , caspase , biochemistry , genetics
Phospholipase A 2 (PLA 2 ) 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 PLA 2 ‐treated cells. Moreover, PLA 2 treatment increased Fas and FasL protein expression. Upon exposure to PLA 2 , 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 PLA 2 and led to prolonged JNK activation, but failed to affect PLA 2 ‐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 PLA 2 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 PLA 2 ‐induced p38 MAPK and JNK activation and p38α MAPK activation suppressed dynamically persistent JNK activation. Downregulation of FADD abolished PLA 2 ‐induced procaspase‐8 degradation and rescued viability of PLA 2 ‐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. J. Cell. Biochem. 109: 245–254, 2010. © 2009 Wiley‐Liss, Inc.