Regulation of homocysteine metabolism and methylation in human and mouse tissues
Regulation of homocysteine metabolism and methylation in human and mouse tissues
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DOI：
10.1096/fj.09-143651
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发表时间：
2010-08-01
期刊：
影响因子：
4.8
通讯作者：
Wang, Hong
中科院分区：
文献类型：
--
作者：
Chen, Natalie C.;Yang, Fan;Wang, Hong
高同型半胱氨酸血症是心血管疾病的独立危险因素。同型半胱氨酸（Hcy）代谢涉及多种酶;然而，组织Hcy代谢及其与甲基化的相关性仍然未知。在这里，我们建立了8个同型半胱氨酸代谢酶和12个甲基化酶在20人和19小鼠组织中的基因表达谱，通过生物信息学分析使用表达序列标签克隆计数在组织cDNA文库。我们分析了小鼠组织中基因表达、Hcy、S-腺苷高半胱氨酸（SAH）和S-腺苷甲硫氨酸（SAM）水平以及SAM/SAH比值之间的相关性。同型半胱氨酸代谢酶和甲基化酶可分为两类。1型酶的表达与组织Hcy和SAH水平呈正相关。这些酶包括胱硫醚β-合酶、胱硫醚-γ-裂解酶、对轴磷酶1，5，10-亚甲基四氢叶酸还原酶、甜菜碱：高半胱氨酸甲基转移酶、甲硫氨酸腺苷转移酶、磷脂酰乙醇胺N-甲基转移酶和甘氨酸N-甲基转移酶。2型酶表达与组织Hcy和SAH水平均不相关。这些酶包括SAH水解酶、甲硫氨酰-tRNA合酶、5-甲基四氢叶酸：Hcy甲基转移酶、S-腺苷甲硫氨酸脱羧酶、DNA甲基转移酶1/3a、异戊二烯基半胱氨酸羧基甲基转移酶和组蛋白-赖氨酸N-甲基转移酶。SAH是唯一与Hcy水平和甲基化酶表达显著相关的Hcy代谢产物。我们建立了表达甲基化酶对组织SAH、SAM和SAM/SAH比率的联合作用的方程。我们的研究是第一个提供全景组织基因表达谱和组织甲基化调控的数学模型。Chen，N. C.的方法，杨，F.，卡佩奇湖M.，顾志，Schafer，A.一、Durante，W.，杨X- F.、Wang，H.人类和小鼠组织中同型半胱氨酸代谢和甲基化的调节。FASEB J.24，2804-2817（2010）。www.fasebj.org
Hyperhomocysteinemia is an independent risk factor for cardiovascular disease. Homocysteine (Hcy) metabolism involves multiple enzymes; however, tissue Hcy metabolism and its relevance to methylation remain unknown. Here, we established gene expression profiles of 8 Hcy metabolic and 12 methylation enzymes in 20 human and 19 mouse tissues through bioinformatic analysis using expression sequence tag clone counts in tissue cDNA libraries. We analyzed correlations between gene expression, Hcy, S-adenosylhomocysteine (SAH), and S-adenosylmethionine (SAM) levels, and SAM/SAH ratios in mouse tissues. Hcy metabolic and methylation enzymes were classified into two types. The expression of Type 1 enzymes positively correlated with tissue Hcy and SAH levels. These include cystathionine beta-synthase, cystathionine-gamma-lyase, paraxonase 1, 5,10-methylenetetrahydrofolate reductase, betaine: homocysteine methyltransferase, methionine adenosyltransferase, phosphatidylethanolamine N-methyltransferases and glycine N-methyltransferase. Type 2 enzyme expressions correlate with neither tissue Hcy nor SAH levels. These include SAH hydrolase, methionyl-tRNA synthase, 5-methyltetrahydrofolate:Hcy methyltransferase, S-adenosylmethionine decarboxylase, DNA methyltransferase 1/3a, isoprenylcysteine carboxyl methyltransferases, and histone-lysine N-methyltransferase. SAH is the only Hcy metabolite significantly correlated with Hcy levels and methylation enzyme expression. We established equations expressing combined effects of methylation enzymes on tissue SAH, SAM, and SAM/SAH ratios. Our study is the first to provide panoramic tissue gene expression profiles and mathematical models of tissue methylation regulation.-Chen, N. C., Yang, F., Capecci, L. M., Gu, Z., Schafer, A. I., Durante, W., Yang, X.-F., Wang, H. Regulation of homocysteine metabolism and methylation in human and mouse tissues. FASEB J. 24, 2804-2817 (2010). www.fasebj.org