title: Dimethyl sulfoxide attenuates nitric oxide generation via modulation of cationic amino acid transporter-1 in human umbilical vein endothelial cells.
abstract: Dimethyl sulfoxide (DMSO) is a solvent that is commonly used in medicine. Conflicting data exist as to its effects on endothelial function. Endothelial cell dysfunction (ECD) is characterized by decreased endothelial nitric oxide synthase (eNOS) activity. Cationic amino acid transporter-1 (CAT-1), the specific arginine transporter for eNOS, has been shown to modulate eNOS activity. We hypothesize that DMSO inhibits eNOS activity through modulation of its selective arginine supplier CAT-1. We studied the effect of DMSO on arginine transport, NO2/NO3 generation as an index of NO production, as well as CAT-1 and Protein Kinase C alpha (PKC-α) (CAT-1 inhibitor) protein expression in human umbilical vein endothelial cell cultures (HUVECs). DMSO 2.5% and 3.5% (v/v) significantly attenuated arginine transport, a phenomenon which was prevented by co-incubation with l-arginine (1 mM). The aforementioned findings were accompanied by a decrease in NO2/NO3 generation. DMSO significantly increased the abundance of phosphorylated CAT-1 (the inactive form) and phosphorylated PKC-α protein, an effect that was attenuated by l-arginine. GO 6976 (PKC-α antagonist) prevented the decrease in arginine transport caused by DMSO. DMSO also induced profound transient morphological changes in HUVECs' structure but these were not related to its effect on arginine transport. In conclusion, DMSO inhibits NO generation by endothelial cells through modulation of CAT-1 activity.
authors.affiliation: Department of Nephrology, Tel Aviv Sourasky Medical Center, Tel Aviv University, Sackler School of Medicine, Tel Aviv, Israel.
authors.forename: Ohad S
authors.initials: OS
authors.lastname: Bentur
authors.affiliation: Department of Nephrology, Tel Aviv Sourasky Medical Center, Tel Aviv University, Sackler School of Medicine, Tel Aviv, Israel.
authors.forename: Tamara
authors.initials: T
authors.lastname: Chernichovski
authors.affiliation: Department of Nephrology, Tel Aviv Sourasky Medical Center, Tel Aviv University, Sackler School of Medicine, Tel Aviv, Israel.
authors.forename: Merav
authors.initials: M
authors.lastname: Ingbir
authors.affiliation: Department of Nephrology, Tel Aviv Sourasky Medical Center, Tel Aviv University, Sackler School of Medicine, Tel Aviv, Israel.
authors.forename: Talia
authors.initials: T
authors.lastname: Weinstein
authors.affiliation: Department of Nephrology, Tel Aviv Sourasky Medical Center, Tel Aviv University, Sackler School of Medicine, Tel Aviv, Israel. Electronic address: idit.francesca@gmail.com.
authors.forename: Idit F
authors.initials: IF
authors.lastname: Schwartz
mesh_terms: D027201:Cationic Amino Acid Transporter 1 / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects*; D006801:Humans; D009569:Nitric Oxide / Q000096:biosynthesis*; D052250:Nitric Oxide Synthase Type III / Q000187:drug effects / Q000378:metabolism
chemical_list: D027201:Cationic Amino Acid Transporter 1; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D004121:Dimethyl Sulfoxide
keywords: Arginine transport; CAT-1; Cytoskeleton; DMSO; Endothelial function; HUVEC; Nitric oxide; PKC-α