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Mol. Cells 2010; 29(2): 203-208

Published online February 28, 2010

https://doi.org/DOI/10.1007/s10059-009-0183-z

© The Korean Society for Molecular and Cellular Biology

Upregulation of Cytosolic NADP+-Dependent Isocitrate Dehydrogenase by Hyperglycemia
Protects Renal Cells Against Oxidative Stress

Soh-Hyun Lee1, Sun-Ok Ha1, Ho-Jin Koh1, KilSoo Kim2, Seon-Min Jeon3, Myung-Sook Choi3, Oh-Shin Kwon1, and Tae-Lin Huh1,4,*

Received: November 4, 2009; Accepted: November 10, 2009

Abstract

Hyperglycemia-induced oxidative stress is widely recog-nized 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 upre-gulation 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 anti-oxidant thiol proteins.

Keywords NADP+-dependent isocitrate dehydrogenase (IDPc), diabetic nephropathy, hyperglycemia, NADPH, oxidative stress

Article

Research Article

Mol. Cells 2010; 29(2): 203-208

Published online February 28, 2010 https://doi.org/DOI/10.1007/s10059-009-0183-z

Copyright © The Korean Society for Molecular and Cellular Biology.

Upregulation of Cytosolic NADP+-Dependent Isocitrate Dehydrogenase by Hyperglycemia
Protects Renal Cells Against Oxidative Stress

Soh-Hyun Lee1, Sun-Ok Ha1, Ho-Jin Koh1, KilSoo Kim2, Seon-Min Jeon3, Myung-Sook Choi3, Oh-Shin Kwon1, and Tae-Lin Huh1,4,*

Received: November 4, 2009; Accepted: November 10, 2009

Abstract

Hyperglycemia-induced oxidative stress is widely recog-nized 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 upre-gulation 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 anti-oxidant thiol proteins.

Keywords: NADP+-dependent isocitrate dehydrogenase (IDPc), diabetic nephropathy, hyperglycemia, NADPH, oxidative stress

Mol. Cells
Aug 31, 2022 Vol.45 No.8, pp. 513~602
COVER PICTURE
Cryo-EM structure of human porphyrin transporter ABCB6 (main figure) shows that binding of hemin (inset, magenta) in concert with two glutathione molecules (cyan) primes ABCB6 for high ATP turnover (Kim et al., pp. 575-587).

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