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Arachidonic acid peroxides induce apoptotic Neuro-2A cell death in association with intracellular Ca(2+) rise and mitochondrial damage independently of caspase-3 activation.

Abstract
The present study aimed at understanding the effects of arachidonic acid peroxides on neuronal cell death using the mouse neuroblastoma cell line, Neuro-2A cells. Arachidonic acid peroxides were produced by ultraviolet (UV) radiation. UV-radiated arachidonic acid significantly reduced Neuro-2A cell viability at concentrations of more than 0.1 muM, with being more potential than non-radiated arachidonic acid. Nuclei of Neuro-2A cells killed with UV-radiated arachidonic acid were reactive to Hoechst 33342, a marker of apoptosis, and the effect was much greater than that achieved with non-radiated arachidonic acid. UV-radiated arachidonic acid persistently increased intracellular Ca(2+) concentrations and dissipated mitochondrial membrane potential in Neuro-2A cells. UV-radiated arachidonic acid-induced Neuro-2A cell death, whereas it was not affected by a pancaspase inhibitor or a caspase-3 inhibitor, was significantly inhibited by an inhibitor of caspase-1, -8, or -9. The results of the present study suggest that arachidonic acid peroxides induce apoptotic neuronal cell death in association with intracellular Ca(2+) rise and mitochondrial damage, in part via a caspase-dependent pathway regardless of caspase-3.
AuthorsMasaru Saitoh, Kaoru Nagai, Takahiro Yaguchi, Yoshiko Fujikawa, Keiko Ikejiri, Satoshi Yamamoto, Kazuhiko Nakagawa, Takehira Yamamura, Tomoyuki Nishizaki
JournalBrain research (Brain Res) Vol. 991 Issue 1-2 Pg. 187-94 (Nov 21 2003) ISSN: 0006-8993 [Print] Netherlands
PMID14575891 (Publication Type: Comparative Study, Journal Article)
Chemical References
  • Enzyme Inhibitors
  • Lipid Peroxides
  • Arachidonic Acid
  • Casp3 protein, mouse
  • Caspase 3
  • Caspases
  • Calcium
Topics
  • Animals
  • Apoptosis (drug effects, physiology)
  • Arachidonic Acid (metabolism, radiation effects)
  • Calcium (metabolism)
  • Caspase 3
  • Caspases (metabolism)
  • Cell Line, Tumor
  • Enzyme Activation
  • Enzyme Inhibitors (pharmacology)
  • Fluorescent Antibody Technique
  • Intracellular Fluid (drug effects, metabolism)
  • Lipid Peroxides (pharmacology)
  • Membrane Potentials (drug effects, physiology)
  • Mice
  • Mitochondria (drug effects, pathology)

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