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

✍ Scribed by Ku-Chung Chen; Pei-Hsiu Kao; Shinne-Ren Lin; Long-Sen Chang

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: English
• Weight: 457 KB
• Volume: 106
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.21979

✦ Synopsis

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 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. J. Cell. Biochem. 106: 93–102, 2009. © 2008 Wiley‐Liss, Inc.