Linoleic Acid Derivative DCP-LA Protects Neurons from Oxidative Stress-Induced Apoptosis by Inhibiting Caspase-3/-9 Activation

Abstract

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.

Intrastrain Comparison of the Chemical Composition and Antioxidant Activity of an Edible Mushroom,Pleurotus giganteus, and Its Potent Neuritogenic Properties

“…Linoleic acid was found to protect mouse cortical neurons against glutamate excitotoxicity [48]. Linoleic acid and its derivatives also prevented sodium nitroprusside-induced cell death of cultured rat cerebral cortical neurons [49]. However, to date, limited information is available on the role of polyunsaturated fatty acid as a stimulator of NGF synthesis in neuronal cells.…”

α, β-DCP-LA Selectively Activates PKC-ε and Stimulates Neurotransmitter Release with the Highest Potency among 4 Diastereomers

“…DCP-LA, on the other hand, is capable of protecting neurons from oxidative stress-induced apoptosis by inhibiting caspase-3/-9 activation [8]. This, in the light of the fact that oxidative stress-induced neuronal apoptosis is a critical factor for pathogenesis of neurodegenerative diseases such as Alzheimer disease and Parkinson disease [9][10][11], further supports the possibility that DCP-LA could be developed as a promising drug for treatment of neurodegenerative diseases including Alzheimer disease.…”

DCP-LA Exerts an Antiaging Action on the Skin

“…One would think that H 2 O 2 treatment is more physiological to induce oxidative stress than SNP treatment. We have confirmed that SNP induces oxidative stress, thereby activating caspase-3 and -9 responsible for neuronal cell death, and that DCP-LA neutralizes the effect of SNP [21]. To induce oxidative stress, therefore, SNP was used in the present experiments.…”

“…We have earlier synthesized the linoleic acid derivative 8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA), which contains cyclopropane rings instead of cis -double bonds on linoleic acid. We have found that DCP-LA inhibits oxidative stress-induced apoptosis of neurons by inhibiting caspase-3/-9 activation [21]. Then, we were prompted to assess the effect of DCP-LA on oxidative stress-induced skin damage.…”