title: Taurine reduces nitrosative stress and nitric oxide synthase expression in high glucose-exposed human Schwann cells.
abstract: The role of taurine in regulating glucose-induced nitrosative stress has been examined in human Schwann cells, a model for understanding the pathogenesis of diabetic neuropathy. Exposure to high glucose increased nitrated proteins (1.56 fold p<0.05), inducible nitric oxide synthase (iNOS) and neuronal NOS (nNOS) mRNA expression (1.55 fold and 2.2 fold respectively, p<0.05 both), phospho-p38 MAPK (1.32 fold, p<0.05) abundance and decreased Schwann cell growth (11±2%, p<0.05). Taurine supplementation prevented high-glucose induced iNOS and nNOS mRNA upregulation, reduced nitrated proteins and phospho-p38 MAPK (56±11% and 45±18% (p<0.05 both) respectively) and restored Schwann cell growth to control levels. High glucose and taurine treatment alone reduced phospho-p42/44 MAPK and phospho-AKT to below detectable levels. Treatment of human Schwann cells with donors of nitric oxide and peroxynitrite reduced taurine transporter (TauT) expression (by 35±5% and 29±7% respectively p<0.05 both) as well as the maximum velocity of taurine uptake (TauT Vmax). NOS inhibition prevented glucose-mediated TauT mRNA downregulation, and restored TauT Vmax. These data demonstrate an important role for taurine in the prevention of nitrosative stress in human Schwann cells, which may have important implications for the development and treatment of diabetic neuropathy.
authors.affiliation: School of Clinical and Experimental Medicine, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: Trevor
authors.initials: T
authors.lastname: Askwith
authors.forename: Wei
authors.initials: W
authors.lastname: Zeng
authors.forename: Margaret C
authors.initials: MC
authors.lastname: Eggo
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Stevens
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D048289:Imidazolidines / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009566:Nitrates / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D015538:Nitrosation / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D012583:Schwann Cells / Q000187:drug effects*; D013654:Taurine / Q000378:metabolism / Q000494:pharmacology*; D008063:Thioctic Acid / Q000494:pharmacology; D000099247:Taurine Transporters
chemical_list: D000975:Antioxidants; D004791:Enzyme Inhibitors; D005947:Glucose; D048289:Imidazolidines; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D008981:Molsidomine; D009566:Nitrates; D020030:Nitric Oxide Donors; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D009599:Nitroprusside; D012333:RNA, Messenger; D013654:Taurine; D008063:Thioctic Acid; D000099247:Taurine Transporters; C002385:linsidomine; C026411:sorbinil