Docosahexaenoic Acid Suppresses Oxidative Stress‐Induced Autophagy and Cell Death via the AMPK‐Dependent Signaling Pathway in Immortalized Fischer Rat Schwann Cells 1

Abstract

Autophagy is the process by which intracellular components are degraded by lysosomes. It is also activated by oxidative stress; hence, autophagy is thought to be closely related to oxidative stress, one of the major causes of diabetic neuropathy. We previously reported that docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) induced antioxidant enzymes and protected Schwann cells from oxidative stress. However, the relationship between autophagy and oxidative stress‐in-duced cell death in diabetic neuropathy has not been elucidated. Treatment with tert‐butyl hydrop-eroxide (tBHP) decreased the cell survival rate, as measured by an MTT assay in immortalized Fischer rat Schwann cells 1 (IFRS1). A DHA pretreatment significantly prevented tBHP‐induced cytotoxicity. tBHP increased autophagy, which was revealed by the ratio of the initiation markers, AMP‐activated protein kinase, and UNC51‐like kinase phosphorylation. Conversely, the DHA pre-treatment suppressed excessive tBHP‐induced autophagy signaling. Autophagosomes induced by tBHP in IFRS1 cells were decreased to control levels by the DHA pretreatment whereas autolyso-somes were only partially decreased. These results suggest that DHA attenuated excessive autoph-agy induced by oxidative stress in Schwann cells and may be useful to prevent or reduce cell death in vitro. However, its potentiality to treat diabetic neuropathy must be validated in in vivo studies.