European Journal of Nutrition

, Volume 52, Issue 5, pp 1461–1473 | Cite as

Alpha-lipoic acid upregulates antioxidant enzyme gene expression and enzymatic activity in diabetic rat kidneys through an O-GlcNAc-dependent mechanism

  • Jelena Arambašić
  • Mirjana Mihailović
  • Aleksandra Uskoković
  • Svetlana Dinić
  • Nevena Grdović
  • Jelena Marković
  • Goran Poznanović
  • Djordje Bajec
  • Melita Vidaković
Original Contribution

Abstract

Purpose

The combined hyperglycemia lowering and antioxidant actions of α-lipoic acid (LA) contribute to its usefulness in preventing renal injury and other diabetic complications. The precise mechanisms by which LA alters diabetic oxidative renal injury are not known. We hypothesized that LA through its hypoglycemic effect lowers O-GlcNAcylation which influences the expression and activities of antioxidant enzymes which assume important roles in preventing diabetes-induced oxidative renal injury.

Methods

An experimental model of diabetes was induced in rats by the administration of 40 mg/kg streptozotocin (STZ) intraperitoneally (i.p.) for five consecutive days. LA was applied at a dose of 10 mg/kg i.p. for 4 weeks, starting from the last day of STZ administration.

Results

An improved glycemic status of LA-treated diabetic rats was accompanied by a significant suppression of oxidative stress and a reduction of oxidative damage of lipids, proteins and DNA. LA treatment normalized CuZn-superoxide dismutase (SOD) and catalase activities in renal tissue of diabetic rats. These changes were allied with upregulated gene expression and lower levels of O-GlcNA glycosylation. The accompanying increase in MnSOD activity was only linked with upregulated gene expression. The observed antioxidant enzyme gene regulation was accompanied by nuclear translocation of Nuclear factor-erythroid-2-related factor 2 (Nrf2), enhanced expression of heat shock proteins (HSPs) and by reduction in O-GlcNAcylation of HSP90, HSP70, and extracellular regulated kinase and p38.

Conclusion

α-Lipoic acid administration activates a coordinated cytoprotective response against diabetes-induced oxidative injury in kidney tissue through an O-GlcNAc-dependent mechanism.

Keywords

Diabetes Kidney α-Lipoic acid O-GlcNAc modification Antioxidant enzymes 

Notes

Acknowledgments

This work was supported by the Ministry of Education, Science and Technological Development of the Republic of Serbia, Grant No. 173020.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Jelena Arambašić
    • 1
  • Mirjana Mihailović
    • 1
  • Aleksandra Uskoković
    • 1
  • Svetlana Dinić
    • 1
  • Nevena Grdović
    • 1
  • Jelena Marković
    • 1
  • Goran Poznanović
    • 1
  • Djordje Bajec
    • 2
  • Melita Vidaković
    • 1
  1. 1.Department of Molecular Biology, Institute for Biological ResearchUniversity of BelgradeBelgradeSerbia
  2. 2.Medical Faculty, Clinical Center of SerbiaUniversity of BelgradeBelgradeSerbia

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