Omega-3 polyunsaturated fatty acids exert anti-oxidant effects through the nuclear factor (erythroid-derived 2)-related factor 2 pathway in immortalized mouse Schwann cells

Aims/Introduction Recent studies advocate that omega-3 polyunsaturated fatty acids (omega-3 PUFAs) have direct anti-oxidative and anti-inflammatory effects in the vasculature; however, the role of omega-3 PUFAs in Schwann cells remains undetermined. Materials and methods Immortalized mouse Schwann (IMS32) cells were incubated with the omega-3 PUFAs docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). The messenger ribonucleic acid levels of several anti-oxidant enzymes (heme oxygenase-1 [Ho-1], nicotinamide adenine dinucleotide [phosphate] H quinone oxidoreductase 1, catalase, superoxide dismutase and glutathione peroxidase) were identified using real-time reverse transcription polymerase chain reaction. Ho-1 and nicotinamide adenine dinucleotide [phosphate] H quinone oxidoreductase 1 protein levels were evaluated using Western blotting. Nuclear factor (erythroid-derived 2)-related factor 2 (Nrf2) of the nuclear fraction was also quantified using western blotting. Catalase activity and glutathione content were determined by colorimetric assay kits. Nrf2 promoter-luciferase activity was evaluated by a dual luciferase assay system. Results Treatment with tert-butyl hydroperoxide decreased cell viability dose-dependently. DHA or EPA pretreatment significantly alleviated tert-butyl hydroperoxide-induced cytotoxicity. DHA or EPA increased the messenger ribonucleic acid levels of Ho-1, nicotinamide adenine dinucleotide (phosphate) H quinone oxidoreductase 1 and catalase dose-dependently. Ho-1 protein level, catalase activity, Nrf2 promoter-luciferase activity and intracellular glutathione content were significantly increased by DHA and EPA. Conclusions These findings show that DHA and EPA can induce Ho-1 and catalase through Nrf2, thus protecting Schwann cells against oxidative stress. omega-3 PUFAs appear to exert their neuroprotective effect by increasing defense mechanisms against oxidative stress in diabetic neuropathies.