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

Full Abstract

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 x min(-1) x 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 alpha-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.

Author information

Author/s: Askwith, Trevor (T); Zeng, Wei (W); Eggo, Margaret C (MC); Stevens, Martin J (MJ);

Affiliation: Dept. of Clinical and Experimental Medicine, Univ. of Birmingham, Birmingham, B15 2TT UK.

Grants: R01-AT-2146-04 (Agency:NCCAM NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: American journal of physiology. Endocrinology and metabolism (Am J Physiol Endocrinol Metab), published in United States. (Language: eng)

Reference: 2009-Sep; vol 297 (issue 3) : pp E620-8

Dates: Created 2009/08/19; Completed 2009/09/30;

PMID: 19602579, status: MEDLINE (last retrieval date: 9/30/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

External Links for this article
(including full text providers, if available):

Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.

This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.

MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Glucose - pharmacology
Humans
Hyperglycemia - complications; genetics; metabolism; pathology
Membrane Glycoproteins - genetics; metabolism
Membrane Transport Proteins - genetics; metabolism
Oxidative Stress - drug effects; physiology
Schwann Cells - drug effects; metabolism; pathology
Taurine - metabolism

Associated Chemicals: Antioxidants (0) ; Enzyme Inhibitors (0) ; Membrane Glycoproteins (0) ; Membrane Transport Proteins (0) ; Taurine (107-35-7) ; taurine transporter (148686-53-7) ; Glucose (50-99-7) ; Aldehyde Reductase (EC 1.1.1.21)

These are the highest related articles currently in the database: