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Molecular and Cellular Biochemistry

, Volume 393, Issue 1–2, pp 111–122 | Cite as

Redox regulation of antioxidant enzymes: post-translational modulation of catalase and glutathione peroxidase activity by resveratrol in diabetic rat liver

  • Gökhan Sadi
  • Davut Bozan
  • Huseyin Bekir Yildiz
Article

Abstract

Resveratrol is a strong antioxidant that exhibits blood glucose-lowering effects, which might contribute to its usefulness in preventing complications associated with diabetes. The present study aimed to investigate resveratrol effects on catalase (CAT) and glutathione peroxidase (GPx) gene and protein expression, their phosphorylation states and activities in rat liver of STZ-induced diabetes. Diabetes increased the levels of total protein phosphorylation and p-CAT, while mRNA expression, protein levels, and activity were reduced. Although diabetes induced transcriptional repression over GPx, it did not affect the protein levels and activity. When resveratrol was administered to diabetic rats, an increase in activity was associated with an increase in p-GPx levels. Decrease in Sirtuin1 (SIRT1) and nuclear factor erythroid 2-related factor (Nrf2) and increase in nuclear factor kappa B (NFκB) gene expression in diabetes were associated with a decrease in CAT and GPx mRNA expression. A possible compensatory mechanism for reduced gene expression of antioxidant enzymes is proved to be nuclear translocation of redox-sensitive Nrf2 and NFκB in diabetes which is confirmed by the increase in nuclear and decrease in cytoplasmic protein levels of Nrf2 and NFκB. Taken together, these findings revealed that an increase in the oxidized state in diabetes intricately modified the cellular phosphorylation status and regulation of antioxidant enzymes. Gene regulation of antioxidant enzymes was accompanied by nuclear translocation of Nrf2 and NFκB. Resveratrol administration also activated a coordinated cytoprotective response against diabetes-induced changes in liver tissues.

Keywords

Diabetes Protein phosphorylation Resveratrol Catalase Glutathione peroxidase 

Abbreviations

CAT

Catalase

GPx

Glutathione peroxidase

STZ

Streptozotocin

p-CAT

Phosphorylated catalase

p-GPx

Phosphorylated glutathione peroxidase

qRT-PCR

Quantitative real-time PCR

SIRT1

Sirtuin1

Nrf2

Nuclear factor erythroid 2-related factor

NFκB

Nuclear factor kappa B

ROS

Reactive oxygen species

GR

Glutathione reductase

GSH

Reduced glutathione

PAGE

Sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis

HRP

Horseradish peroxidase

PTPs

Protein tyrosine phosphatases

TBARS

Thiobarbituric acid reactive substances

Notes

Acknowledgments

Financial support provided by grants obtained from Karamanoglu Mehmetbey University (BAP-27-M-12) and TUBITAK (112T159) is gratefully acknowledged.

Conflict of Interest

The authors declare no conflict of interest.

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Gökhan Sadi
    • 1
  • Davut Bozan
    • 1
  • Huseyin Bekir Yildiz
    • 2
    • 3
  1. 1.Department of BiologyKaramanoglu Mehmetbey UniversityKaramanTurkey
  2. 2.Department of ChemistryKaramanoglu Mehmetbey UniversityKaramanTurkey
  3. 3.Department of ChemistryMiddle East Technical UniversityAnkaraTurkey

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