Asymmetric Dimethylarginine, an Endogenous NOS Inhibitor, Is Actively Metabolized in Rat Erythrocytes

作者：Yokoro Miyuki; Suzuki Makiko; Murota Kaeko; Otsuka Chie; Yamashita Hiromi; Takahashi Yoshitaka; Tsuji Hideaki; Kimoto Masumi^*

来源：Bioscience Biotechnology and Biochemistry, 2012, 76(7): 1334-1342.

DOI：10.1271/bbb.120086

• asymmetric dimethylarginine
• endogenous inhibitor of nitric oxide synthase (NOS)
• risk factor for atherosclerosis
• catalase
• protein arginine methylation

N-G, N-G-Dimethyl-L-arginine (asymmetric dimethylarginine: ADMA) is an endogenous competitive inhibitor of nitric oxide synthase (NOS). Plasma ADMA concentrations have been reported to increase in connection with diseases associated with an impaired endothelial L-arginine/NO pathway. In this study, we investigated the metabolism of ADMA in circulating blood cell populations to elucidate the regulatory mechanism of elevation of plasma ADMA, a novel risk factor for cardiovascular disease. We found by RT-PCR and Western blot analyses that protein arginine methyltransferase (PRMT)1 and dimethylarginine dimethylaminohydrolase (DDAH)-1, responsible for the biosynthesis and degradation of ADMA respectively, are expressed in erythrocytes (ECs), leukocytes, and platelets. We also identified a major ADMA-containing protein in ECs as catalase, confirmed by GST-pull down assay to bind to PRMT1 in vitro. This is the first report that the ADMA-metabolizing system, including the arginine methylation of proteins and the breakdown of free ADMA, occurs in circulating blood cell-populations, and that catalase in ECs might be a potential protein targeted by PRMT1.

• 出版日期2012-7