Published online Oct 18, 2018. doi: 10.4331/wjbc.v9.i1.1
Peer-review started: July 30, 2018
First decision: August 24, 2018
Revised: September 19, 2018
Accepted: October 11, 2018
Article in press: October 12, 2018
Published online: October 18, 2018
Processing time: 82 Days and 2.6 Hours
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 pancreatic β-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 lipid-metabolizing capacity via the activation of peroxisome proliferator-activated receptors represent promising therapeutics for NAFLD.
Core tip: Accumulated experimental data indicate that oxidative stress causes endoplasmic reticulum stress, which together leads to pathogenic damage to cells. The lipid metabolism in the liver is a sensitive target of these types of stress, which appears to be associated with non-alcoholic fatty liver disease.