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

被引：64

作者：

Zhang, Xinhao ^{[1
]}

Jiang, Liping ^{[2
]}

Chen, Huangben ^{[1
]}

Wei, Sen ^{[3
]}

Yao, Kun ^{[4
]}

Sun, Xiance ^{[3
]}

Yang, Guang ^{[1
]}

Jiang, Lijie ^{[5
]}

Zhang, Cong ^{[1
]}

Wang, Ningning ^{[1
]}

Wang, Yan ^{[6
]}

Liu, Xiaofang ^{[1
]}

机构：

[1] Dalian Med Univ, Coll Publ Hlth, Dept Nutr & Food Safety, 9 West Segment South Ivshun Rd, Dalian 116044, Liaoning, Peoples R China

[2] Dalian Med Univ, Coll Publ Hlth, Prevent Med Lab, 9 West Segment South Ivshun Rd, Dalian 116044, Liaoning, Peoples R China

[3] Dalian Med Univ, Coll Publ Hlth, Dept Occupat & Environm Hlth, 9 West Segment South Ivshun Rd, Dalian 116044, Liaoning, Peoples R China

[4] Dalian Med Univ, Affiliated Hosp 2, Dept Orthoped, Dalian 116023, Peoples R China

[5] Dalian Univ, Afliated Zhong Shan Hosp, Dept Internal Med, Dalian 116001, Liaoning, Peoples R China

[6] Second Hosp Chaoyang, Dept Endocrinol, 26 Chaoyang St Twin Towers, Chaoyang 122000, Peoples R China

来源：

TOXICOLOGY | 2022年 / 465卷

关键词：

Acrolein; Ferroptosis; Resveratrol; MIN6; cells; Endoplasmic reticulum stress; PROLIFERATOR-ACTIVATED RECEPTORS; ENDOPLASMIC-RETICULUM STRESS; UNFOLDED PROTEIN RESPONSE; MECHANISMS; METABOLISM; EXPRESSION; APOPTOSIS; EXTRACT; HEALTH; PPARS;

D O I：

10.1016/j.tox.2021.153048

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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.

引用

页数：12