Arachidonic acid-induced apoptosis of human neuroblastoma SK-N-SH cells is mediated through mitochondrial alteration elicited by ROS and Ca2+-evoked activation of p38α MAPK and JNK1

Ku Chung Chen, Long Sen Chang

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

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 (ΔΨm). 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, ΔΨm loss and ROS generation. N-Acetylcysteine (ROS scavenger) pretreatment reduced the dissipation of ΔΨm, 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 p38α 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 p38α MAPK and JNK1.

Original languageEnglish
Pages (from-to)199-206
Number of pages8
JournalToxicology
Volume262
Issue number3
DOIs
Publication statusPublished - Aug 21 2009
Externally publishedYes

Keywords

  • Apoptosis
  • Arachidonic acid
  • JNK1
  • Mitochondrial alteration
  • p38α MAPK
  • Reactive oxygen species

ASJC Scopus subject areas

  • Toxicology

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