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

• Published in: Journal of diabetes investigation Vol. 10; no. 3; pp. 602 - 612
• Main Authors: Tatsumi, Yasuaki, Kato, Ayako, Sango, Kazunori, Himeno, Tatsuhito, Kondo, Masaki, Kato, Yoshiro, Kamiya, Hideki, Nakamura, Jiro, Kato, Koichi
• Format: Journal Article
• Language: English
• Published: Japan John Wiley & Sons, Inc 01.05.2019; John Wiley and Sons Inc; Wiley
• Subjects: Adenine; Animals; Antioxidants - metabolism; Apoptosis; Butyl hydroperoxide; Catalase; Cell viability; Colorimetry; Cytotoxicity; Deoxyribonucleic acid; Diabetes; Diabetes mellitus; Diabetic neuropathy; DNA; Docosahexaenoic acid; Eicosapentaenoic acid; Enzymes; Fatty acids; Fatty Acids, Omega-3 - pharmacology; Gene Expression Regulation, Enzymologic - drug effects; Glutathione - metabolism; Glutathione peroxidase; Heme; Hyperglycemia; Inflammation; Kinases; Mice; NADPH; Neuroprotection; NF-E2-Related Factor 2 - metabolism; Nicotinamide; NRF2 protein; Omega‐3 polyunsaturated fatty acids; Original; Oxidation-Reduction; Oxidative stress; Oxidative Stress - drug effects; Oxidoreductase; Oxygenase; Pharmaceuticals; Polymerase chain reaction; Polyunsaturated fatty acids; Proteins; Schwann Cells - drug effects; Schwann Cells - metabolism; Studies; Superoxide dismutase; Western blotting; United Kingdom > UK; Ann Arbor Michigan; United States > US; Japan; Oxidative stress; Diabetic neuropathy; Omega-3 polyunsaturated fatty acids
• ISSN: 2040-1116; 2040-1124
• DOI: 10.1111/jdi.12931

Aims/Introduction Recent studies advocate that omega‐3 polyunsaturated fatty acids (ω‐3 PUFAs) have direct anti‐oxidative and anti‐inflammatory effects in the vasculature; however, the role of ω‐3 PUFAs in Schwann cells remains undetermined. Materials and methods Immortalized mouse Schwann (IMS32) cells were incubated with the ω‐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. ω‐3 PUFAs appear to exert their neuroprotective effect by increasing defense mechanisms against oxidative stress in diabetic neuropathies. We demonstrated that both DHA and EPA could prevent cell death by inducing numerous antioxidants in IMS32 cells. Our findings suggest that enhancements of antioxidative defenses might have therapeutic value in the treatment of diabetic neuropathy.