all-trans-retinoic acid increases nitric oxide synthesis by endothelial cells -: A role for the induction of dimethylarginine dimethylaminohydrolase
all-trans-retinoic acid increases nitric oxide synthesis by endothelial cells -: A role for the induction of dimethylarginine dimethylaminohydrolase
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DOI：
10.1161/01.res.0000014450.40853.2b
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发表时间：
2002-04-19
影响因子：
20.1
通讯作者：
Vallance, P
中科院分区：
文献类型：
--
作者：
Achan, V;Tran, CTL;Vallance, P
全反式维甲酸（atRA）对心血管系统的发育和成熟具有重要作用。一氧化氮（NO）的产生与atRA诱导的神经元细胞分化有关，我们假设NO也可能介导atRA在心血管系统中的某些作用。我们研究了ATRA对内皮细胞NO生成的影响，并确定是否负责不对称二甲基精氨酸（ADMA）代谢的酶的调节有助于所看到的效果。将鼠内皮瘤（sEnd.1）细胞与或不与atRA一起孵育。使用Griess反应测定亚硝酸盐的产生。北方印迹法检测NO合酶（NOS）和二甲基精氨酸二甲氨基水解酶（DDAH）基因的表达。还使用报告基因测定来研究atRA对DDAH II启动子的影响。atRA显着增加sEnd.1细胞的亚硝酸盐的生产，尽管没有增加eNOS的表达。atRA还增加DDAH Il基因表达和启动子活性，并降低培养基中ADMA与对称二甲基精氨酸（SDMA）的比率。DDAH抑制剂4124W显著降低atRA诱导的NO合成。本研究表明，atRA增加内皮细胞中NO的合成，而不增加eNOS的表达。atRA还增加DDAH II的表达，DDAH II是内皮细胞中主要的DDAH同种型。我们的数据表明，诱导NO合成的atRA可能是由DDAH II促进这一途径可能有助于解释一些atRA对心血管系统的影响。
all-trans-Retinoic acid (atRA) has important effects on the developing and mature cardiovascular system. Nitric oxide (NO) production has been associated with the atRA-induced differentiation of neuronal cells, and we hypothesized that NO may also mediate certain actions of atRA in the cardiovascular system. We studied the effects of atRA on NO production by endothelial cells and determined whether regulation of enzymes responsible for metabolism of asymmetric dimethylarginine (ADMA) contributed to the effects seen. Murine endothelioma (sEnd.1) cells were incubated with or without atRA. Nitrite production was determined using the Griess reaction. The expression of NO synthase (NOS) and dimethylarginine dimethylaminohydrolase (DDAH) genes was determined by Northern blotting. A reporter gene assay was also used to study the effect of atRA on the DDAH II promoter. atRA significantly increased nitrite production by sEnd.1 cells despite no increase in eNOS expression. atRA also increased DDAH Il gene expression and promoter activity and reduced the ratio of ADMA to symmetric dimethylarginine (SDMA) in culture medium. The DDAH inhibitor 4124W significantly reduced the induction of NO synthesis by atRA. The present study demonstrates that atRA increases NO synthesis in endothelial cells without increasing eNOS expression. atRA also increases the expression of DDAH II, the predominant DDAH isoform in endothelial cells. Our data suggests that the induction of NO synthesis by atRA may be facilitated by DDAH II This pathway may help to explain some of the effects of atRA on the cardiovascular system.