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

Journal of Cellular Biochemistry
Ku-Chung ChenLong-Sen Chang

Abstract

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 p38alpha MAPK proved that ASK1 pathway was responsible for PLA(2)-induced p38 MAPK and JNK activation and p38alpha MAPK activation suppressed dynamically persistent JNK ac...Continue Reading

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Mar 9, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Konrad Kamil HusAleksandra Bocian

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