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Homocysteine enhances cell proliferation in vascular smooth muscle cells: role of p38 MAPK and p47phox

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收录情况: ◇ SCIE ◇ 统计源期刊 ◇ CSCD-C

机构: [1]Department of Cardiology, Beijing Hospital, Beijing 100730, China [2]Department of Obstetrics, the First Affiliated Hospital, Kunming Medical College, Kunming 650032, China [3]Research Laboratory Center, Yan’an Hospital, Kunming Medical College, Kunming, 650051, China
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关键词: homocysteine NAD(P)H oxidase vascular smooth muscle cell p47phox p38 MAPK

摘要:
Elevation of blood homocysteine levels (hyperhomocysteinemia) is a risk factor for cardiovascular disorders. One of the mechanisms by which homocysteine induces atherosclerosis is to promote the proliferation of vascular smooth muscle cells (VSMCs) in a reactive oxygen species (ROS)-dependent manner. It has been shown that homocysteine induces the production of ROS through the activation of NAD(P)H oxidases in VSMCs. In this study, we investigated the signal transduction pathways involved in the activation of NAD(P)H oxidases. Homocysteine promoted DNA synthesis in VSMCs. Inhibition of ROS by N-acetyl-l-cysteine (an antioxidant) and apocynin (an inhibitor of NAD(P)H oxidases) significantly blocked homocysteine-induced proliferation in VSMCs. Homocysteine induced a rapid increase in the phosphorylation of p38-mitogen-activated protein kinase (p38 MAPK). p38 MAPK in turn activated NAD(P)H oxidases by inducing the phosphorylation of p47phox, resulting in the generation of ROS. ROS induced the phosphorylation of Akt, which was probably responsible for proliferation in VSMCs. These findings demonstrate that homocysteine induces an increase in the activity of NAD(P)H oxidases in VSMCs by activating p38 MAPK and enhancing the phosphorylation of p47phox.

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出版当年[2011]版:
大类 | 4 区 生物
小类 | 4 区 生化与分子生物学 4 区 生物物理
最新[2023]版:
大类 | 2 区 生物学
小类 | 2 区 生物物理 3 区 生化与分子生物学
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出版当年[2010]版:
Q4 BIOPHYSICS Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
最新[2023]版:
Q1 BIOPHYSICS Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2010版] 出版当年五年平均 出版前一年[2009版] 出版后一年[2011版]

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第一作者机构: [1]Department of Cardiology, Beijing Hospital, Beijing 100730, China
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