Cargando…
Recombinant Human Thioredoxin-1 Protects Macrophages from Oxidized Low-Density Lipoprotein-Induced Foam Cell Formation and Cell Apoptosis
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 effe...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Korean Society of Applied Pharmacology
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5839490/ https://www.ncbi.nlm.nih.gov/pubmed/28554199 http://dx.doi.org/10.4062/biomolther.2016.275 |
_version_ | 1783304420313792512 |
---|---|
author | Zhang, Hui Liu, Qi Lin, Jia-Le Wang, Yu Zhang, Ruo-Xi Hou, Jing-Bo Yu, Bo |
author_facet | Zhang, Hui Liu, Qi Lin, Jia-Le Wang, Yu Zhang, Ruo-Xi Hou, Jing-Bo Yu, Bo |
author_sort | Zhang, Hui |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5839490 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | The Korean Society of Applied Pharmacology |
record_format | MEDLINE/PubMed |
spelling | pubmed-58394902018-03-07 Recombinant Human Thioredoxin-1 Protects Macrophages from Oxidized Low-Density Lipoprotein-Induced Foam Cell Formation and Cell Apoptosis Zhang, Hui Liu, Qi Lin, Jia-Le Wang, Yu Zhang, Ruo-Xi Hou, Jing-Bo Yu, Bo Biomol Ther (Seoul) Original Article 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. The Korean Society of Applied Pharmacology 2018-03 2017-05-30 /pmc/articles/PMC5839490/ /pubmed/28554199 http://dx.doi.org/10.4062/biomolther.2016.275 Text en Copyright © 2018 The Korean Society of Applied Pharmacology http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Zhang, Hui Liu, Qi Lin, Jia-Le Wang, Yu Zhang, Ruo-Xi Hou, Jing-Bo Yu, Bo Recombinant Human Thioredoxin-1 Protects Macrophages from Oxidized Low-Density Lipoprotein-Induced Foam Cell Formation and Cell Apoptosis |
title | Recombinant Human Thioredoxin-1 Protects Macrophages from Oxidized Low-Density Lipoprotein-Induced Foam Cell Formation and Cell Apoptosis |
title_full | Recombinant Human Thioredoxin-1 Protects Macrophages from Oxidized Low-Density Lipoprotein-Induced Foam Cell Formation and Cell Apoptosis |
title_fullStr | Recombinant Human Thioredoxin-1 Protects Macrophages from Oxidized Low-Density Lipoprotein-Induced Foam Cell Formation and Cell Apoptosis |
title_full_unstemmed | Recombinant Human Thioredoxin-1 Protects Macrophages from Oxidized Low-Density Lipoprotein-Induced Foam Cell Formation and Cell Apoptosis |
title_short | Recombinant Human Thioredoxin-1 Protects Macrophages from Oxidized Low-Density Lipoprotein-Induced Foam Cell Formation and Cell Apoptosis |
title_sort | recombinant human thioredoxin-1 protects macrophages from oxidized low-density lipoprotein-induced foam cell formation and cell apoptosis |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5839490/ https://www.ncbi.nlm.nih.gov/pubmed/28554199 http://dx.doi.org/10.4062/biomolther.2016.275 |
work_keys_str_mv | AT zhanghui recombinanthumanthioredoxin1protectsmacrophagesfromoxidizedlowdensitylipoproteininducedfoamcellformationandcellapoptosis AT liuqi recombinanthumanthioredoxin1protectsmacrophagesfromoxidizedlowdensitylipoproteininducedfoamcellformationandcellapoptosis AT linjiale recombinanthumanthioredoxin1protectsmacrophagesfromoxidizedlowdensitylipoproteininducedfoamcellformationandcellapoptosis AT wangyu recombinanthumanthioredoxin1protectsmacrophagesfromoxidizedlowdensitylipoproteininducedfoamcellformationandcellapoptosis AT zhangruoxi recombinanthumanthioredoxin1protectsmacrophagesfromoxidizedlowdensitylipoproteininducedfoamcellformationandcellapoptosis AT houjingbo recombinanthumanthioredoxin1protectsmacrophagesfromoxidizedlowdensitylipoproteininducedfoamcellformationandcellapoptosis AT yubo recombinanthumanthioredoxin1protectsmacrophagesfromoxidizedlowdensitylipoproteininducedfoamcellformationandcellapoptosis |