Asymmetric Dimethylarginine, an Endogenous NOS Inhibitor, Is Actively Metabolized in Rat Erythrocytes
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概要
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NG,NG-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.
著者
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Kimoto Masumi
Department Of Nutritional Science Faculty Of Health And Welfare Okayama Prefectural University
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Suzuki Makiko
Department Of Hematology And Rheumatology Tohoku University Hospital
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Tsuji Hideaki
Department Of Chemistry Faculty Of Education Gifu University
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Yamashita Hiromi
Department Of Applied Chemistry College Of Engineering Osaka Prefecture University
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Murota Kaeko
Department Of Food Science Graduate School Of Nutrition And Bioscience The University Of Tokushima
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Yokoro Miyuki
Department Of Nutritional Science Faculty Of Health And Welfare Science Okayama Prefectural Universi
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Takahashi Yoshitaka
Department Of Applied Physics Faculty Of Engineering University Of Tokyo
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Otsuka Chie
Department Of Biochemistry Shujitsu University School Of Pharmacy
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Suzuki Makiko
Department of Nutritional Science, Faculty of Health and Welfare Science, Okayama Prefectural University
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Kimoto Masumi
Department of Immunology and Host Defenses, Ehime University Graduate School of Medicine
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MUROTA Kaeko
Department of Life Science, School of Science and Engineering, Kinki University
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