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Homocysteine promotes proliferation and activation of microglia

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机构： [1]Laboratory for Conservation and Utilization of Bio-Resources, Yunnan University, Kunming, Yunnan 650091, China [2]Department of Biochemistry, Kunming Medical College, Kunming, Yunnan 650031, China [3]Department of Cardiology, the First Affiliated Hospital, Kunming Medical College, Kunming, Yunnan 650032, China

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关键词： Homocysteine Microglia Proliferation Activation NAD(P)H oxidases Reactive oxygen species p47phox p38 MAPK

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Epidemiological and experimental studies have correlated hyperhomocysteinemia to a range of neurodegenerative conditions, including Alzheimer's disease, stroke, and Parkinson's disease. Although homocysteine-induced apoptosis in neurons has been extensively studied, little information is available regarding the effect of homocysteine on microglia. In this report, we demonstrated that homocysteine promoted proliferation and up-regulated the expression of CD11b (a marker of microglial activation). Consistent with our in vitro results, a significant increase in the number of CD11b-positive microglia was also observed in brain sections of mice with hyperhomocysteinemia. Homocysteine promoted the activity of NAD(P)H oxidases, resulting in the generation of reactive oxygen species. Up-regulation of NAD(P)H oxidase activity by homocysteine appears to be due to its ability to induce the phosphorylation of p47phox through the p38 MAPK pathway. Furthermore, inhibition of reactive oxygen species significantly blocked cellular proliferation and activation in microglia. Since microglial proliferation and activation play an important role in the development of several neurodegenerative disorders, our results reveal a novel role of homocysteine in the pathogenesis of neurodegenerative diseases. (C) 2008 Elsevier Inc. All rights reserved.

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出版当年[2011]版：

大类 | 2 区医学

小类 | 2 区老年医学 2 区神经科学

最新[2023]版：

大类 | 3 区医学

小类 | 3 区老年医学 3 区神经科学

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出版当年[2010]版：

Q1 GERIATRICS & GERONTOLOGY Q1 NEUROSCIENCES

最新[2023]版：

Q2 GERIATRICS & GERONTOLOGY Q2 NEUROSCIENCES

影响因子： 3.7 最新[2023版] 4.1 最新五年平均 6.634 出版当年[2010版] 6.438 出版当年五年平均 5.937 出版前一年[2009版] 6.189 出版后一年[2011版]

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第一作者机构： [1]Laboratory for Conservation and Utilization of Bio-Resources, Yunnan University, Kunming, Yunnan 650091, China

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