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 |
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Authors: | Ku‐Chung Chen Pei‐Hsiu Kao Shinne‐Ren Lin Long‐Sen Chang |
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Affiliation: | 1. Institute of Biomedical Sciences, National Sun Yat‐Sen University‐Kaohsiung Medical University Joint Research Center, National Sun Yat‐Sen University, Kaohsiung 804, Taiwan;2. Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung 807, Taiwan |
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Abstract: | 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 A2 (PLA2). Upon exposure to PLA2, p38 MAPK activation, ERK inactivation, ROS generation, increase in intracellular Ca2+ 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 (Ca2+ 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 PLA2‐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 PLA2‐induced cell death is, in part, elicited by upregulation of Fas and FasL, which is regulated by Ca2+‐ and ROS‐evoked p38 MAPK activation, and suggest that non‐catalytic PLA2 plays a role for the signaling pathway. J. Cell. Biochem. 106: 93–102, 2009. © 2008 Wiley‐Liss, Inc. |
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Keywords: | phospholipase A2 ROS Ca2+ p38 MAPK activation Fas/FasL upregulation |
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