title: JNK1/c-Jun and p38 alpha MAPK/ATF-2 pathways are responsible for upregulation of Fas/FasL in human chronic myeloid leukemia K562 cells upon exposure to Taiwan cobra phospholipase A2.
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 p38 alpha MAPK and JNK1 by siRNA proved that p38 alpha MAPK and JNK1 were involved in ATF-2 and c-Jun phosphorylation, respectively. Compared with the p38 alpha 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 p38 alpha MAPK/ATF-2 and JNK1/c-Jun pathways in K562 cells, and PLA(2) catalytic activity is involved in this action.
authors: Institute of Biomedical Sciences, National Sun Yat-Sen University-Kaohsiung Medical University Joint Research Center, Kaohsiung 804, Taiwan.
authors: Ku-Chung
authors: KC
authors: Chen
authors: Yi-Ling
authors: YL
authors: Chiou
authors: Long-Sen
authors: LS
authors: Chang
mesh_terms: D051698:Activating Transcription Factor 2 / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D020013:Calcium Signaling / Q000187:drug effects; D017815:Elapidae; D004789:Enzyme Activation / Q000187:drug effects; D053222:Fas Ligand Protein / Q000378:metabolism*; D006801:Humans; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000201:enzymology* / Q000473:pathology; D008244:Lysophosphatidylcholines / Q000494:pharmacology; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism; D054467:Phospholipases A2 / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013624:Taiwan; D015854:Up-Regulation / Q000187:drug effects; D019014:fas Receptor / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: C497105:ATF2 protein, human; D051698:Activating Transcription Factor 2; C491901:FAS protein, human; D053222:Fas Ligand Protein; D008244:Lysophosphatidylcholines; D016755:Proto-Oncogene Proteins c-jun; D017382:Reactive Oxygen Species; D019014:fas Receptor; D048055:Mitogen-Activated Protein Kinase 8; D048051:p38 Mitogen-Activated Protein Kinases; D054467:Phospholipases A2