二甲基精氨酸-二甲胺水解酶2的表达、调节和功能

Dimethylarginine Dimethylaminohydrolase 2: Expression,Regulation and Function

非对称性-二甲基精氨酸(ADMA)抑制一氧化氮合酶,是内皮功能损伤、心血管疾病的危险因素。二甲基精氨酸-二甲胺水解酶(DDAH)可以代谢ADMA,主要分为两种。DDAH-1主要分布于肾小管、肝脏,从循环中摄取ADMA;DDAH-2主要存在于血管中,分布于内皮细胞胞膜交界处及胞内颗粒、血管平滑肌细胞肌纤维及核被膜中。肾和血管中的DDAH,其表达调节和分布均具有特异性,可以特异地调节一氧化氮(NO)的产生。下面主要介绍DDAH-2的表达、调节与功能,描述了DDAH-2在NO产生、内皮功能中所起的作用。

Asymmetric（ NG,NG） -dimethylarginine（ ADMA） inhibits nitric oxide（ NO） synthases. ADMA is a risk factor for endothelial dysfunction,cardiovascular mortality,and the progression of chronic kidney disease. Two isoforms of dimethylarginine dimethylaminohydrolase（ DDAH） metabolize ADMA. DDAH-1 is the predominant isoform existing in the proximal tubules of the kidney and in the liver. These organs take ADMA from the circulation. DDAH-2 is the predominant isoform in the vasculature,where it is found in endothelial cells adjacent to the cell membrane,intracellular vesicles and vascular smooth muscle cells among the myofibrils and the nuclear envelope. DDAH-2 is also expressed in the renal macula densa and distal nephron. In this review,the recent advances in the regulation and function of DDAH-2 enzymes,their roles in the regulation of NO generation,and its possible contribution to endothelial dysfunction are summarized.