Upregulation of Fas and FasL in Taiwan cobra phospholipase A2-treated human neuroblastoma SK-N-SH cells through ROS- and Ca2+-mediated p38 MAPK activation.
The aim of the present study is to elucidate the signaling pathway involved in death of human neuroblastoma SK-N-SH cells induced by Naja naja atra phospholipase A(2) (PLA(2)). Upon exposure to PLA(2), p38 MAPK activation, ERK inactivation, ROS generation, increase in intracellular Ca(2+) concentration, and upregulation of Fas and FasL were found in SK-N-SH cells. SB202190 (p38MAPK inhibitor) suppressed upregulation of Fas and FasL. N-Acetylcysteine (ROS scavenger) and BAPTA-AM (Ca(2+) chelator) abrogated p38 MAPK activation and upregulation of Fas and FasL expression, but restored phosphorylation of ERK. Activated ERK was found to attenuate p38 MAPK-mediated upregulation of Fas and FasL. Deprivation of catalytic activity could not diminish PLA(2)-induced cell death and Fas/FasL upregulation. Moreover, the cytotoxicity of arachidonic acid and lysophosphatidylcholine was not related to the expression of Fas and FasL. Taken together, our results indicate that PLA(2)-induced cell death is, in part, elicited by upregulation of Fas and FasL, which is regulated by Ca(2+)- and ROS-evoked p38 MAPK activation, and suggest that non-catalytic PLA(2) plays a role for the signaling pathway.
Chen
Ku-Chung
KC
Institute of Biomedical Sciences, National Sun Yat-Sen University-Kaohsiung Medical University Joint Research Center, National Sun Yat-Sen University, Kaohsiung 804, Taiwan.
Kao
Pei-Hsiu
PH
Lin
Shinne-Ren
SR
Chang
Long-Sen
LS
D000818:Animals; D016718:Arachidonic Acid / Q000633:toxicity; D002118:Calcium / Q000378:metabolism*; D045744:Cell Line, Tumor; D004546:Elapid Venoms / Q000201:enzymology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D054467:Phospholipases A2 / Q000633:toxicity*; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D015854:Up-Regulation; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D004546:Elapid Venoms; C491901:FAS protein, human; D053222:Fas Ligand Protein; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D019014:fas Receptor; D016718:Arachidonic Acid; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D054467:Phospholipases A2; D002118:Calcium