机构：[a]Institute of Neuroscience, Soochow University, Suzhou, Jiangsu 215123, China[b]Department of Neurology, The Second Affiliated Hospital of Soochow University, Soochow University, Suzhou, Jiangsu 215021, China[c]Beijing Key Laboratory for Parkinson's Disease, Beijing 100053, China
Recent studies suggest that epigenetic alterations such as DNA methylation control many aspects of monocytes/macrophages and participate in the pathogenesis of atherosclerosis, a lipid-driven inflammatory disorder. Our and other groups demonstrated that dysregulation of cystathionine gamma-lyase (CSE)-hydrogen sulfide (H2S) pathway was involved in monocyte/macrophages-mediated inflammation and atherosclerosis. However, it remains unknown whether altered cse methylation in macrophages may play a role in linking CSE-H2S dysregulation and atherosclerosis. In the present study, we showed that plasma H2S and H2S production in the peritoneal macrophages of apolipoprotein knockout (apoE(-/-)) mice gradually decreased with ages, and were also lower than that in control mice at 12 weeks older. Moreover, CSE mRNA expressions decreased while DNA methyltransferase (DNMT) expressions increased in the peritoneal macrophages isolated from apoE(-/-) mice, compared to age-matched wildtype mice. Similar observations were obtained in an in vitro study. In oxidized low-density lipoprotein (ox-LDL)-treated raw264.7 macrophages, cse transcription was down-regulated while the expression and activity of DNMT was up-regulated, associated with enhanced DNA methylation in cse promoter. Suppression of DNMT with its inhibitor or siRNA reversed the decrease of CSE mRNA. Therefore, our data suggest that DNA hypermethylation of CpG rich region in cse promoter might contribute to the decrease of cse transcription and H2S production in macrophages, and thus contribute to atherosclerosis development. (C) 2015 Elsevier Inc. All rights reserved.
基金：
This work was supported by Science and Education Methodist
Youth Science and Technology Project of Suzhou Health Bureau
(KJXW2011010), Suzhou Science and Technology Development
Program (SYSD2013091), Suzhou Medical Key Discipline Project
and the Priority Academic Program Development of Jiangsu Higher
Education Institutions (PAPD).
第一作者机构：[a]Institute of Neuroscience, Soochow University, Suzhou, Jiangsu 215123, China
共同第一作者：
通讯作者：
通讯机构：[*1]Department of Pharmacology and Institute of Neuroscience, Soochow University, 199 Ren-Ai Road, Suzhou Industrial Park, Suzhou 215123, China.
推荐引用方式(GB/T 7714)：
Hua-Ping Du,Jiaojiao Li,Shou-Jiang You,et al.DNA methylation in cystathionine-gamma-lyase (CSE) gene promoter induced by ox-LDL in macrophages and in apoE knockout mice[J].BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS.2016,469(3):776-82.doi:10.1016/j.bbrc.2015.11.132.
APA：
Hua-Ping Du,Jiaojiao Li,Shou-Jiang You,Ya-LiWang,FenWang...&Chun-Feng Liu.(2016).DNA methylation in cystathionine-gamma-lyase (CSE) gene promoter induced by ox-LDL in macrophages and in apoE knockout mice.BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,469,(3)
MLA：
Hua-Ping Du,et al."DNA methylation in cystathionine-gamma-lyase (CSE) gene promoter induced by ox-LDL in macrophages and in apoE knockout mice".BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 469..3(2016):776-82
