title: Lysophosphatidylcholine-induced elevation of asymmetric dimethylarginine level by the NADPH oxidase pathway in endothelial cells.
abstract: Recent studies suggested that endothelium is a main source of reactive oxygen species (ROS) and the major source was via NADPH oxidase pathway. Various stimuli including lysophosphatidylcholine (LPC), a major component of oxidized low-density lipoprotein (ox-LDL), can enhance the activity of NADPH oxidase and lead to a marked ROS generation. Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide (NO) synthase (NOS) inhibitor, which is synthesized by protein arginine methyltransferase I (PRMT I) and degraded by dimethylarginine dimethylaminohydrolase (DDAH) in endothelial cells. Much evidence showed that ADMA was closely related to endothelial dysfunction. Our previous study showed that LPC elevated ADMA level in endothelial cells via increasing oxidative stress, but the precise cellular mechanism is not defined yet. The present study was to explore the mechanism of NADPH oxidase in LPC-induced elevation of ADMA. In LPC-treated endothelial cells, the ROS production, cell viability, ADMA and NO levels, the activity of DDAH and expression of PRMT I were detected. Treatment with LPC (10 microg/ml) for 24 h markedly increased intracellular ROS production, the expression of PRMT I, level of ADMA, decreased the concentration of NO and the activity of DDAH. These effects were attenuated by diphenyliodonium, the NADPH oxidase inhibitor. In summary, the present results suggested that LPC-induced elevation of ADMA was due to reduction of DDAH activity and the up-regulation of PRMT expression by stimulation of ROS production via NADPH oxidase pathway.
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Xiang-Ya Road #110, Changsha 410078, China.
authors.forename: Su-Jie
authors.initials: SJ
authors.lastname: Jia
authors.forename: De-Jian
authors.initials: DJ
authors.lastname: Jiang
authors.forename: Chang-Ping
authors.initials: CP
authors.lastname: Hu
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Zhang
authors.forename: Han-Wu
authors.initials: HW
authors.lastname: Deng
authors.forename: Yuan-Jian
authors.initials: YJ
authors.lastname: Li
mesh_terms: D000581:Amidohydrolases / Q000378:metabolism; D001120:Arginine / Q000031:analogs & derivatives* / Q000378:metabolism; D001713:Biphenyl Compounds / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects* / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D009861:Onium Compounds / Q000494:pharmacology; D011484:Protein-Arginine N-Methyltransferases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism
chemical_list: D001713:Biphenyl Compounds; D004791:Enzyme Inhibitors; D008244:Lysophosphatidylcholines; D009861:Onium Compounds; D017382:Reactive Oxygen Species; D012097:Repressor Proteins; C031291:diphenyliodonium; D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine; D019255:NADPH Oxidases; C099988:PRMT1 protein, human; D011484:Protein-Arginine N-Methyltransferases; D000581:Amidohydrolases; C059999:dimethylargininase