Resveratrol protected acrolein-induced ferroptosis and insulin secretion dysfunction via ER-stress- related PERK pathway in MIN6 cells

Acrolein is a typical food and environmental pollutant and a risk factor for diabetes. The primary pathogenesis of diabetes is insulin deficiency and resistance. Ferroptosis is an iron-dependent cell death type, accompanying by lipid peroxide accumulation. Here, 25 mu M acrolein-induced ferroptosis is observed in mouse pancreatic beta-cell MIN6 cells as indicated by ferroptosis-related indicators, including GPX4 exhaustion, lipid peroxides accumulation, and insulin secretion impairment. Additionally, acrolein-induced ferroptosis could be reversed by Ferrostatin-1. Furthermore, endoplasmic reticulum stress (ER stress) is involved in acrolein-induced ferroptosis. The ER stress inhibits the expression of PPAR gamma, an essential gene in glucose and lipid metabolism, and facilitates lipid peroxide accumulation, leading to MIN6 cells ferroptosis and dysfunction. Moreover, resveratrol, an antioxidant natural product, may relieve ER stress and upregulate PPAR. expression, thereby inhibiting acrolein-induced ferroptosis. Thus, this study demonstrated a new perspective for the cytotoxic mechanism of acrolein on pancreatic beta-cell and the protective effect of resveratrol.