Arachidonic acid peroxides induce apoptotic Neuro-2A cell death in association with intracellular Ca(2+) rise and mitochondrial damage independently of caspase-3 activation.
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.
Department of Physiology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya 663-8501, Japan.
Masaru
M
Saitoh
Kaoru
K
Nagai
Takahiro
T
Yaguchi
Yoshiko
Y
Fujikawa
Keiko
K
Ikejiri
Satoshi
S
Yamamoto
Kazuhiko
K
Nakagawa
Takehira
T
Yamamura
Tomoyuki
T
Nishizaki
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D016718:Arachidonic Acid / Q000378:metabolism / Q000528:radiation effects*; D002118:Calcium / Q000378:metabolism*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D008054:Lipid Peroxides / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000473:pathology
D004791:Enzyme Inhibitors; D008054:Lipid Peroxides; D016718:Arachidonic Acid; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D002118:Calcium