title: Alpha-lipoic acid activates dimethylarginine dimethylaminohydrolase in cultured endothelial cells.
abstract: Asymmetric dimethylarginine (ADMA) is a risk factor of cardiovascular diseases. alpha-Lipoic acid (ALA) was shown to improve vascular dysfunction, and to decrease plasma ADMA level. In this study, we investigated whether ALA activates dimethylarginine dimethylaminohydrolase (DDAH), the metabolizing enzyme of ADMA, in cultured endothelial cells. ALA significantly decreased ADMA level in culture media of endothelial cells. ALA increased the gene expression and activity of DDAH, and signal transducer and activator of transcription (STAT)3 phosphorylation. Transfection of STAT3 increased DDAH II promoter activity, and ALA amplified it. ALA-induced increase in DDAH II promoter activity was attenuated in the promoter that had mutation in putative STAT3-binding site. These results suggest that ALA reduces ADMA level by enhancing DDAH activity and DDAH II gene expression, thus providing a novel mechanism by which ALA regulates endothelial function.
authors.affiliation: Department of Internal Medicine, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors.forename: Woo Je
authors.initials: WJ
authors.lastname: Lee
authors.forename: Seung-Whan
authors.initials: SW
authors.lastname: Kim
authors.forename: Seung-Hwan
authors.initials: SH
authors.lastname: Kim
authors.forename: Geun Hyang
authors.initials: GH
authors.lastname: Kim
authors.forename: Sung Min
authors.initials: SM
authors.lastname: Han
authors.forename: Jong Chul
authors.initials: JC
authors.lastname: Won
authors.forename: Chang Hee
authors.initials: CH
authors.lastname: Jung
authors.forename: Hye-Sun
authors.initials: HS
authors.lastname: Park
authors.forename: Do Sook
authors.initials: DS
authors.lastname: Choi
authors.forename: Ki-Up
authors.initials: KU
authors.lastname: Lee
authors.forename: Joong-Yeol
authors.initials: JY
authors.lastname: Park
mesh_terms: D000581:Amidohydrolases / Q000235:genetics*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000378:metabolism; D045744:Cell Line, Tumor; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology*; D004790:Enzyme Induction; D051379:Mice; D011401:Promoter Regions, Genetic; D050796:STAT3 Transcription Factor / Q000378:metabolism; D008063:Thioctic Acid / Q000494:pharmacology / Q000502:physiology*
chemical_list: D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; C018524:N,N-dimethylarginine; D008063:Thioctic Acid; D001120:Arginine; D000581:Amidohydrolases; C059999:dimethylargininase