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Recombinant Human Thioredoxin-1 Protects Macrophages from Oxidized Low-Density Lipoprotein-Induced Foam Cell Formation and Cell Apoptosis
Biomolecules & Therapeutics ; : 121-129, 2018.
Artículo en Inglés | WPRIM | ID: wpr-713584
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.
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Texto completo: Disponible Índice: WPRIM (Pacífico Occidental) Asunto principal: Fosforilación / Tiorredoxinas / Colesterol / Muerte Celular / Especies Reactivas de Oxígeno / Apoptosis / Proteínas Quinasas p38 Activadas por Mitógenos / Aterosclerosis / Receptores de LDL Oxidadas / Caspasa 3 Límite: Humanos Idioma: Inglés Revista: Biomolecules & Therapeutics Año: 2018 Tipo del documento: Artículo

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Texto completo: Disponible Índice: WPRIM (Pacífico Occidental) Asunto principal: Fosforilación / Tiorredoxinas / Colesterol / Muerte Celular / Especies Reactivas de Oxígeno / Apoptosis / Proteínas Quinasas p38 Activadas por Mitógenos / Aterosclerosis / Receptores de LDL Oxidadas / Caspasa 3 Límite: Humanos Idioma: Inglés Revista: Biomolecules & Therapeutics Año: 2018 Tipo del documento: Artículo