二甲基精氨酸二甲胺水解酶表达调控及与疾病的关系

Regulation of Dimethylarginine Dimethylaminohydrolase Activity and Implication in Human Diseases

非对称性二甲基精氨酸是一种内源性的一氧化氮合酶抑制剂,可竞争性地抑制一氧化氮合酶活性,减少一氧化氮的生成,并可通过直接诱导氧化应激,参与多种疾病如冠心病、高血压、慢性肾脏疾病、糖尿病和恶性肿瘤的发生发展,是心血管疾病新的风险因子。二甲基精氨酸二甲胺水解酶是代谢灭活非对称性二甲基精氨酸的主要酶。二甲基精氨酸二甲胺水解酶表达下调或活性降低可引起体内非对称性二甲基精氨酸聚集,从而促进非对称性二甲基精氨酸相关疾病的发生发展。本文就二甲基精氨酸二甲胺水解酶的组织分布、功能及调控,以及与疾病关系的研究进展进行综述。

Asymmetric dimethylarginine（ADMA） is an endogenous inhibitor of NO synthase（NOS） and can decrease the production of NO via inhibition of NOS competitively.ADMA is reported to be implicated in the pathophysiological processes of several diseases such as atherosclerosis,hypertension,chronic kidney disease,stroke,diabetes and cancer,and is regarded as a novel cardiovascular risk factor.Dimethylarginine dimethylaminohydrolases（DDAH） are enzymes responsible for inactivation of ADMA.A decrease in DDAH activity may lead to ADMA accumulation and thus promotes the development of ADMA-related diseases.Recent development in tissue distribution,biological function,regulation of DDAH,and implication of DDAH in human diseases are reviewed presently.