Biomol Ther.  2018 Mar;26(2):121-129. 10.4062/biomolther.2016.275.

Recombinant Human Thioredoxin-1 Protects Macrophages from Oxidized Low-Density Lipoprotein-Induced Foam Cell Formation and Cell Apoptosis

• Zhang H
• Liu Q
• Lin JL
• Wang Y
• Zhang RX
• Hou JB
• Yu B

• KMID: 2429051
• DOI: http://doi.org/10.4062/biomolther.2016.275

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.

Keyword

Thioredoxin-1; Foam cell; Apoptosis; Atherosclerosis; p38 MAPK

MeSH Terms

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*
Anisomycin
Caspase 3
Cholesterol
Lipoproteins
Reactive Oxygen Species
Receptors, Oxidized LDL
Thioredoxins
p38 Mitogen-Activated Protein Kinases