Premium
JNK1/c‐Jun and p38α MAPK/ATF‐2 pathways are responsible for upregulation of Fas/FasL in human chronic myeloid leukemia K562 cells upon exposure to Taiwan cobra phospholipase A 2
Author(s) -
Chen KuChung,
Chiou YiLing,
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.22293
Subject(s) - fas ligand , downregulation and upregulation , p38 mitogen activated protein kinases , mapk/erk pathway , k562 cells , microbiology and biotechnology , chemistry , apoptosis , biology , signal transduction , biochemistry , programmed cell death , gene
Abstract Fas and FasL expression upregulation was found in human leukemia K562 cells upon exposure to Naja naja atra phospholipase A 2 (PLA 2 ). PLA 2 treatment induced an increase in intracellular Ca 2+ ([Ca 2+ ]i) and ROS generation levels, leading to activation of p38 MAPK and JNK. Suppression of both p38 MAPK and JNK abrogated Fas and FasL upregulation. Unlike PLA 2 , catalytically inactive PLA 2 treatment did not markedly increase Fas and FasL protein expression, and p38 MAPK activation was exclusively responsible for catalytically inactive PLA 2 ‐induced increase in Fas and FasL protein expression. Knockdown of p38α MAPK and JNK1 by siRNA proved that p38α MAPK and JNK1 were involved in ATF‐2 and c‐Jun phosphorylation, respectively. Compared with the p38α MAPK/ATF‐2 pathway, the JNK1/c‐Jun pathway played a crucial role in Fas/FasL upregulation. Unlike arachidonic acid, lysophosphatidylcholine mimicked the PLA 2 action in inducing Fas/FasL upregulation. Together with the previous finding that c‐Jun and ATF‐2 are involved in transcriptional regulation of Fas and FasL, our data suggest that PLA 2 induces Fas and FasL upregulation through p38α MAPK/ATF‐2 and JNK1/c‐Jun pathways in K562 cells, and PLA 2 catalytic activity is involved in this action. J. Cell. Biochem. 108: 612–620, 2009. © 2009 Wiley‐Liss, Inc.