期刊
TOXICOLOGY
卷 262, 期 3, 页码 199-206出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.tox.2009.06.009
关键词
Arachidonic acid; Apoptosis; p38 alpha MAPK; JNK1; Mitochondrial alteration; Reactive oxygen species
资金
- National Science Council, ROC [NSC95-2320-B110-007-MY3]
- National Sun Yat-Sen University-Kaohsiung Medical University Joint Research Center
Arachidonic acid (AA)-induced apoptosis of human neuroblastoma SK-N-SH cells was characteristic of elevation of intracellular Ca2+ concentration ([Ca2+]i), ROS generation, activation of 38 MAPK and JNK and loss of mitochondrial membrane potential (Delta psi m). Subsequent modulation of Bcl-2 family members and cytochrome c release accompanied with activation of caspase-9 and -3 were involved in the death of SK-N-SH cells. BAPTA-AM (Ca2+ chelator) pretreatment rescued viability of AA-treated cells through abolishing phosphorylation of p38 MAPK and JNK, Delta psi m loss and ROS generation. N-Acetylcysteine (ROS scavenger) pretreatment reduced the dissipation of Delta psi m, but insignificantly affected AA-induced p38 MAPK and JNK activation. SB202190 (p38 MAPK inhibitor) and SP600125 (JNK inhibitor) attenuated mitochondrial depolarization, degradation of Bcl-2/Bcl-xL, and mitochondrial translocation of Bax. Transfection of specific siRNA proved that p38 alpha MAPK and JNK1 were involved in modulating Bcl-2 family proteins. Taken together, our data suggest that the cytotoxicity of AA toward SK-N-SH cells is mediated through mitochondria-dependent death pathway, eliciting by AA-induced ROS generation and Ca2+-evoked activation of p38 alpha MAPK and JNK1. (C) 2009 Published by Elsevier Ireland Ltd.
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