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This Article Full Text Full Text (PDF) All Versions of this Article: 297/3/E620    most recent 00287.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Askwith, T. Articles by Stevens, M. J. PubMed PubMed Citation Articles by Askwith, T. Articles by Stevens, M. J.

Oxidative stress and dysregulation of the taurine transporter in high-glucose-exposed human Schwann cells: implications for pathogenesis of diabetic neuropathy

Department of Clinical and Experimental Medicine, University of Birmingham, Birmingham United Kingdom

Submitted 6 May 2009 ; accepted in final form 30 June 2009

In human Schwann cells, the role of taurine in regulating glucose-induced changes in antioxidant defense systems has been examined. Treatment with high glucose for 7 days induced reactive oxygen species, increased 4-hydroxynoneal adducts (20 ± 5%, P < 0.05) and poly(ADP-ribosyl)ated proteins (40 ± 13%, P < 0.05). Increases in these markers of oxidative stress were reversed by simultaneous incubation in 0.25 mM taurine. Both high glucose and taurine independently increased superoxide dismutase and catalase activity and decreased glutathione levels, but their effects were not additive. Glucose reduced taurine transporter (TauT) mRNA and protein in a dose-dependent manner with maximal decreases of 66 ± 6 and 63 ± 12%, respectively (P < 0.05 both). The V_max for taurine uptake was decreased in 30 mM glucose from 61 ± 5 to 42 ± 3 pmol·min^–1·mg protein^–1 (P < 0.001). Glucose-induced TauT downregulation could be reversed by inhibition of aldose reductase, a pathway that depletes NADPH and increases osmotic stress and protein glycation. TauT protein was increased more than threefold, and the V_max for taurine uptake doubled (P < 0.05 both) by prooxidants. TauT downregulation was reversed both by treatment with the antioxidant -lipoic acid, which increased TauT mRNA by 60% and V_max by 50% (P < 0.05 both), and by the aldose reductase inhibitor sorbinil, which increased TauT mRNA 380% and V_max by 98% (P < 0.01 both). These data highlight the potential therapeutic benefits of taurine supplementation in diabetic complications and provide mechanisms whereby taurine restoration could be achieved in order to prevent or reverse diabetic complications.