Recombinant Human Thioredoxin-1 Protects Macrophages from Oxidized Low-Density Lipoprotein-Induced Foam Cell Formation and Cell Apoptosis.
10.4062/biomolther.2016.275
- Author:
Hui ZHANG
1
;
Qi LIU
;
Jia Le LIN
;
Yu WANG
;
Ruo Xi ZHANG
;
Jing Bo HOU
;
Bo YU
Author Information
1. Department of Cardiology, Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. jingbohou@163.com
- Publication Type:Original Article
- Keywords:
Thioredoxin-1;
Foam cell;
Apoptosis;
Atherosclerosis;
p38 MAPK
- MeSH:
Anisomycin;
Apoptosis*;
Atherosclerosis;
Caspase 3;
Cell Death;
Cholesterol;
Foam Cells*;
Humans*;
Lipoproteins;
Macrophages*;
p38 Mitogen-Activated Protein Kinases;
Phosphorylation;
Reactive Oxygen Species;
Receptors, Oxidized LDL;
Thioredoxins*
- From:Biomolecules & Therapeutics
2018;26(2):121-129
- CountryRepublic of Korea
- Language:English
-
Abstract:
Oxidized low-density lipoprotein (ox-LDL)-induced macrophage foam cell formation and apoptosis play critical roles in the pathogenesis of atherosclerosis. Thioredoxin-1 (Trx) is an antioxidant that potently protects various cells from oxidative stress-induced cell death. However, the protective effect of Trx on ox-LDL-induced macrophage foam cell formation and apoptosis has not been studied. This study aims to investigate the effect of recombinant human Trx (rhTrx) on ox-LDL-stimulated RAW264.7 macrophages and elucidate the possible mechanisms. RhTrx significantly inhibited ox-LDL-induced cholesterol accumulation and apoptosis in RAW264.7 macrophages. RhTrx also suppressed the ox-LDL-induced overproduction of lectin-like oxidized LDL receptor (LOX-1), Bax and activated caspase-3, but it increased the expression of Bcl-2. In addition, rhTrx markedly inhibited the ox-LDL-induced production of intracellular reactive oxygen species (ROS) and phosphorylation of p38 mitogen-activated protein kinases (MAPK). Furthermore, anisomycin (a p38 MAPK activator) abolished the protective effect of rhTrx on ox-LDL-stimulated RAW264.7 cells, and SB203580 (a p38 MAPK inhibitor) exerted a similar effect as rhTrx. Collectively, these findings indicate that rhTrx suppresses ox-LDL-stimulated foam cell formation and macrophage apoptosis by inhibiting ROS generation, p38 MAPK activation and LOX-1 expression. Therefore, we propose that rhTrx has therapeutic potential in the prevention and treatment of atherosclerosis.
