International Journal of Molecular Sciences | |
Homocysteine Triggers Inflammatory Responses in Macrophages through Inhibiting CSE-H2S Signaling via DNA Hypermethylation of CSE Promoter | |
Jiao-Jiao Li2  Qian Li1  Hua-Ping Du2  Ya-Li Wang2  Shou-Jiang You2  Fen Wang2  Xing-Shun Xu2  Jian Cheng1  Yong-Jun Cao2  Chun-Feng Liu2  Li-Fang Hu2  | |
[1]Institute of Neuroscience, Soochow University, Suzhou 215123, China | |
[2] E-Mails: | |
[3]Department of Neurology, Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, the Second Affiliated Hospital of Soochow University, Soochow University, Suzhou 215004, China | |
[4] E-Mails: | |
关键词: homocysteine; cystathionine γ-lyase; hydrogen sulfide; macrophage; DNA methylation; | |
DOI : 10.3390/ijms160612560 | |
来源: mdpi | |
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【 摘 要 】
Hyperhomocysteinemia (HHcy) is an independent risk factor of atherosclerosis and other cardiovascular diseases. Unfortunately, Hcy-lowering strategies were found to have limited effects in reducing cardiovascular events. The underlying mechanisms remain unclear. Increasing evidence reveals a role of inflammation in the pathogenesis of HHcy. Homocysteine (Hcy) is a precursor of hydrogen sulfide (H2S), which is formed via the transsulfuration pathway catalyzed by cystathionine β-synthase and cystathionine γ-lyase (CSE) and serves as a novel modulator of inflammation. In the present study, we showed that methionine supplementation induced mild HHcy in mice, associated with the elevations of TNF-α and IL-1β in the plasma and reductions of plasma H2S level and CSE expression in the peritoneal macrophages. H2S-releasing compound GYY4137 attenuated the increases of TNF-α and IL-1β in the plasma of HHcy mice and Hcy-treated raw264.7 cells while CSE inhibitor PAG exacerbated it. Moreover, the
【 授权许可】
CC BY
© 2015 by the authors; licensee MDPI, Basel, Switzerland.
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