title: Symmetric dimethylarginine alters endothelial nitric oxide activity in glomerular endothelial cells.
abstract: Circulating symmetric dimethylarginine (SDMA) is increased in patients with chronic kidney disease. SDMA is considered an inert metabolite, but because it can transported into cells, we studied the effect of SDMA on glomerular endothelial cells. SDMA suppressed VEGF-induced endothelial nitric oxide synthase (eNOS) phosphorylation and nitric oxide production, but not VEGFR2 activation and signaling leading to eNOS activation. SDMA caused eNOS uncoupling and increased superoxide anion production in response to VEGF. All these effects were blocked by preventing cellular uptake of SDMA with a molar excess of arginine. These data show that SDMA interferes with nitric oxide production by uncoupling eNOS and leads to oxidative stress in glomerular endothelial cells. In conclusion, our data show that SDMA is not an inert metabolite and that it could contribute to oxidative stress in the renal endothelium.
authors.affiliation: Department of Medicine/Nephrology, The University of Texas health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA. Electronic address: feliers@uthscsa.edu.
authors.forename: Denis
authors.initials: D
authors.lastname: Feliers
authors.affiliation: Department of Medicine/Nephrology, The University of Texas health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
authors.forename: Duck-Yoon
authors.initials: DY
authors.lastname: Lee
authors.affiliation: Department of Medicine/Nephrology, The University of Texas health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
authors.forename: Yves
authors.initials: Y
authors.lastname: Gorin
authors.affiliation: Department of Medicine/Nephrology, The University of Texas health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
authors.forename: Balakuntalam S
authors.initials: BS
authors.lastname: Kasinath
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D002460:Cell Line; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000166:cytology*; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D055503:Protein Multimerization / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism; D050916:TRPV Cation Channels / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D050916:TRPV Cation Channels; C446923:Trpv6 protein, mouse; D042461:Vascular Endothelial Growth Factor A; D013481:Superoxides; D009569:Nitric Oxide; C024917:symmetric dimethylarginine; D001120:Arginine; D052250:Nitric Oxide Synthase Type III; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: Glomerular endothelial cells; Kidney; Nitric oxide; Oxidative stress; Symmetric dimethylarginine