Mutual interaction between oxidative stress and endoplasmic reticulum stress in the pathogenesis of diseases specifically focusing on non-alcoholic fatty liver disease

• 作者: Han Geuk Seo Junichi Fujii Sho Kobayashi Takujiro Homma
• 来源期刊: 世界生物化学杂志：英文版（电子版）
• 学科: 医学
• 关键词: Oxidative STRESS REACTIVE oxygen species Endoplasmic reticulum STRESS NONALCOHOLIC FATTY liver disease PEROXISOME proliferator-activated receptor
• 年，卷（期）: 2018,（1）
• 页码范围: 1-15
• 页数: 15页
• 分类号: R

摘要

Reactive oxygen species(ROS)are produced during normal physiologic processes with the consumption of oxygen.While ROS play signaling roles,when they are produced in excess beyond normal antioxidative capacity this can cause pathogenic damage to cells.The majority of such oxidation occurs in polyunsaturated fatty acids and sulfhydryl group in proteins,resulting in lipid peroxidation and protein misfolding,respectively.The accumulation of misfolded proteins in the endoplasmic reticulum(ER)is enhanced under conditions of oxidative stress and results in ER stress,which,together,leads to the malfunction of cellular homeostasis.Multiple types of defensive machinery are activated in unfolded protein response under ER stress to resolve this unfavorable situation.ER stress triggers the malfunction of protein secretion and is associated with a variety of pathogenic conditions including defective insulin secretion from pancreaticβ-cells and accelerated lipid droplet formation in hepatocytes.Herein we use nonalcoholic fatty liver disease(NAFLD)as an illustration of such pathological liver conditions that result from ER stress in association with oxidative stress.Protecting the ER by eliminating excessive ROS via the administration of antioxidants or by enhancing lipidmetabolizing capacity via the activation of peroxisome proliferator-activated receptors represent promising therapeutics for NAFLD.