Asymmetric dimethylarginine, an endogenous NOS inhibitor, is actively metabolized in rat erythrocytes.
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.
Department of Nutritional Science, Faculty of Health and Welfare Science, Okayama Prefectural University, Soja, Okayama, Japan.
Miyuki
M
Yokoro
Makiko
M
Suzuki
Kaeko
K
Murota
Chie
C
Otsuka
Hiromi
H
Yamashita
Yoshitaka
Y
Takahashi
Hideaki
H
Tsuji
Masumi
M
Kimoto
D000581:Amidohydrolases / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000378:metabolism*; D004912:Erythrocytes / Q000166:cytology / Q000201:enzymology*; D015870:Gene Expression; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D011485:Protein Binding; D011484:Protein-Arginine N-Methyltransferases / Q000235:genetics* / Q000378:metabolism; D051381:Rats
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine; D002374:Catalase; D019001:Nitric Oxide Synthase; C541817:PRMT1 protein, rat; D011484:Protein-Arginine N-Methyltransferases; D000581:Amidohydrolases; C059999:dimethylargininase