2. Academic Validation
  3. Resveratrol protected acrolein-induced ferroptosis and insulin secretion dysfunction via ER-stress- related PERK pathway in MIN6 cells

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

  • Toxicology. 2022 Jan 15;465:153048. doi: 10.1016/j.tox.2021.153048.
Xinhao Zhang 1,  Liping Jiang 2,  Huangben Chen 1,  Sen Wei 3,  Kun Yao 4,  Xiance Sun 3,  Guang Yang 1,  Lijie Jiang 5,  Cong Zhang 1,  Ningning Wang 1,  Yan Wang 6,  Xiaofang Liu 7
Affiliations

Affiliations

  • 1 Department of Nutrition and Food Safety, College of Public Health, Dalian Medical University, No. 9, West Segment of South lvshun Road, Dalian, 116044, Liaoning, PR China.
  • 2 Preventive Medicine Laboratory, College of Public Health, Dalian Medical University, No. 9, West Segment of South lvshun Road, Dalian, 116044, Liaoning, PR China.
  • 3 Department of Occupational and Environmental Health, College of Public Health, Dalian Medical University. No. 9, West Segment of South lvshun Road, Dalian, 116044, Liaoning, PR China.
  • 4 Department of Orthopedics, the Second Affiliated Hospital of Dalian Medical University, Dalian, 116023, China.
  • 5 Department of Internal Medicine, The Afliated Zhong Shan Hospital of Dalian University, Dalian, 116001, Liaoning, PR China.
  • 6 Department of Endocrinology, the Second Hospital of Chaoyang, No. 26, Chaoyang Street of the Twin Towers, Chaoyang, 122000, China. Electronic address: wangyancy@sohu.com.
  • 7 Department of Nutrition and Food Safety, College of Public Health, Dalian Medical University, No. 9, West Segment of South lvshun Road, Dalian, 116044, Liaoning, PR China. Electronic address: food@dmu.edu.cn.
PMID: 34813903 DOI: 10.1016/j.tox.2021.153048
Abstract

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 μM acrolein-induced Ferroptosis is observed in mouse pancreatic β-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 PPARγ, 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 PPARγ expression, thereby inhibiting acrolein-induced Ferroptosis. Thus, this study demonstrated a new perspective for the cytotoxic mechanism of acrolein on pancreatic β-cell and the protective effect of resveratrol.

Keywords

Acrolein; Endoplasmic reticulum stress; Ferroptosis; MIN6 cells; Resveratrol.

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