Biomolecules & Therapeutics  
Recombinant Human Thioredoxin-1 Protects Macrophages from Oxidized Low-Density Lipoprotein-Induced Foam Cell Formation and Cell Apoptosis
Hui Zhang, Qi Liu, Jia-Le Lin, Yu Wang, Ruo-Xi Zhang, Jing-Bo Hou*and Bo Yu
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
E-mail: jingbohou@163.com
Tel: +86-0451-866051, Fax: +86-0451-8660-5180
Received: December 13, 2016; Revised: February 6, 2017; Accepted: February 7, 2017; Published online: May 30, 2017.
© The Korean Society of Applied Pharmacology. All rights reserved.

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.
Keywords: Thioredoxin-1, Foam cell, Apoptosis, Atherosclerosis, p38 MAPK


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