Molecules and Cells

, Volume 29, Issue 2, pp 203–208 | Cite as

Upregulation of cytosolic NADP+-dependent isocitrate dehydrogenase by hyperglycemia protects renal cells against oxidative stress

  • Soh-Hyun Lee
  • Sun-Ok Ha
  • Ho-Jin Koh
  • KilSoo Kim
  • Seon-Min Jeon
  • Myung-Sook Choi
  • Oh-Shin Kwon
  • Tae-Lin Huh
Article
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Abstract

Hyperglycemia-induced oxidative stress is widely recognized as a key mediator in the pathogenesis of diabetic nephropathy, a complication of diabetes. We found that both expression and enzymatic activity of cytosolic NADP+-dependent isocitrate dehydrogenase (IDPc) were upregulated in the renal cortexes of diabetic rats and mice. Similarly, IDPc was induced in murine renal proximal tubular OK cells by high hyperglycemia, while it was abrogated by co-treatment with the antioxidant N-Acetyl-Cysteine (NAC). In OK cells, increased expression of IDPc by stable transfection prevented hyperglycemia-mediated reactive oxygen species (ROS) production, subsequent cellular oxidative stress and extracellular matrix accumulation, whereas these processes were all stimulated by decreased IDPc expression. In addition, production of NADPH and GSH in the cytosol was positively correlated with the expression level of IDPc in OK cells. These results together indicate that upregulation of IDPc in response to hyperglycemia might play an essential role in preventing the progression of diabetic nephropathy, which is accompanied by ROS-induced cellular damage and fibrosis, by providing NADPH, the reducing equivalent needed for recycling reduced glutathione and low molecular weight antioxidant thiol proteins.

Keywords

cytosolic NADP+-dependent isocitrate dehydrogenase (IDPc) diabetic nephropathy hyperglycemia NADPH oxidative stress 
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Copyright information

© The Korean Society for Molecular and Cellular Biology and Springer Netherlands 2010

Authors and Affiliations

  • Soh-Hyun Lee
    • 1
  • Sun-Ok Ha
    • 1
  • Ho-Jin Koh
    • 1
  • KilSoo Kim
    • 2
  • Seon-Min Jeon
    • 3
  • Myung-Sook Choi
    • 3
  • Oh-Shin Kwon
    • 1
  • Tae-Lin Huh
    • 1
    • 4
  1. 1.School of Life Sciences and BiotechnologyKyungpook National UniversityDaeguKorea
  2. 2.College of Veterinary MedicineKyungpook National UniversityDaeguKorea
  3. 3.Department of Food Science and NutritionKyungpook National UniversityDaeguKorea
  4. 4.TG Biotech Research Institute, TechnobuildingKyungpook National UniversityDaeguKorea

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