Linoleic acid derivative DCP-LA protects neurons from oxidative stress-induced apoptosis by inhibiting caspase-3/-9 activation.
The present study aimed at understanding the effect of the linoleic acid derivative 8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA) on oxidative stress-induced neuronal death. Sodium nitroprusside (SNP; 1 mM) reduced viability of cultured rat cerebral cortical neurons to 50% of basal levels, but DCP-LA significantly prevented the SNP effect in a concentration (1-100 nM)-dependent manner. In addition, DCP-LA (100 nM) rescued neurons from SNP-induced degradation. SNP (1 mM) activated caspase-3 and -9 in cultured rat cerebral cortical neurons, but DCP-LA (100 nM) abolished the caspase activation. For a mouse model of middle cerebral artery occlusion, oral administration with DCP-LA (1 mg/kg) significantly diminished degraded area due to cerebral infarction. The results of the present study, thus, demonstrate that DCP-LA protects neurons at least in part from oxidative stress-induced apoptosis by inhibiting activation of caspase-3/-9.
Yaguchi
Takahiro
T
Division of Bioinformation, Department of Physiology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, 663-8501, Japan.
Fujikawa
Hirokazu
H
Nishizaki
Tomoyuki
T
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002545:Brain Ischemia / Q000517:prevention & control; D002210:Caprylates / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism*; D053453:Caspase 9 / Q000378:metabolism*; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy; D008297:Male; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D009599:Nitroprusside / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats
C506022:8-(2-(2-pentyl-cyclopropylmethyl)cyclopropyl)octanoic acid; D002210:Caprylates; D009599:Nitroprusside; D053148:Caspase 3; D053453:Caspase 9