Redox dependence of glomerular epithelial cell hypertrophy in response to glucose

Nam Ho Kim, Hernan Rincon-Choles, Basant Bhandari, Goutam Ghosh-choudhury, Hanna E. Abboud, Yves Gorin

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Podocytes or glomerular epithelial cells (GECs) are important targets of the diabetic microenvironment. Podocyte foot process effacement and widening, loss of GECs and hypertrophy are pathological features of this disease. ANG II and oxidative stress are key mediators of renal hypertrophy in diabetes. The cellular mechanisms responsible for GEC hypertrophy in diabetes are incompletely characterized. We investigated the effect of high glucose on protein synthesis and GEC hypertrophy. Exposure of GECs to high glucose dose dependently stimulated [3H]leucine incorporation, but not [3H] yhymidine incorporation. High glucose resulted in the activation of ERK1/2 and Akt/PKB. ERK1/2 pathway inhibitor or the dominant negative mutant of Akt/PKB inhibited high glucose-induced protein synthesis. High glucose elicited a rapid generation of reactive oxygen species (ROS). The stimulatory effect of high glucose on ROS production, ERK1/2, and Akt/PKB activation was prevented by the antioxidants catalase, diphenylene iodonium, and N-acetylcysteine. Exposure of the cells to hydrogen peroxide mimicked the effects of high glucose. In addition, ANG II resulted in the activation of ERK1/2 and Akt/PKB and GEC hypertrophy. Moreover, high glucose and ANG II exhibited additive effects on ERK1/2 and Akt/PKB activation as well as protein synthesis. These additive responses were abolished by treatment of the cells with the antioxidants. These data demonstrate that high glucose stimulates GEC hypertrophy through a ROS-dependent activation of ERK1/2 and Akt/PKB. Enhanced ROS generation accounts for the additive effects of high glucose and ANG II, suggesting that this signaling cascade contributes to GEC injury in diabetes.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Renal Physiology
Volume290
Issue number3
DOIs
StatePublished - Mar 2006

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Hypertrophy
Oxidation-Reduction
Epithelial Cells
Glucose
Reactive Oxygen Species
Podocytes
Antioxidants
Proteins
MAP Kinase Signaling System
Acetylcysteine
Leucine
Catalase
Hydrogen Peroxide
Oxidative Stress
Kidney
Wounds and Injuries

Keywords

  • Angiotensin II
  • High glucose
  • Hypertrophy
  • Podocytes
  • Protein synthesis
  • Reactive oxygen species

ASJC Scopus subject areas

  • Physiology

Cite this

Redox dependence of glomerular epithelial cell hypertrophy in response to glucose. / Kim, Nam Ho; Rincon-Choles, Hernan; Bhandari, Basant; Ghosh-choudhury, Goutam; Abboud, Hanna E.; Gorin, Yves.

In: American Journal of Physiology - Renal Physiology, Vol. 290, No. 3, 03.2006.

Research output: Contribution to journalArticle

Kim, Nam Ho ; Rincon-Choles, Hernan ; Bhandari, Basant ; Ghosh-choudhury, Goutam ; Abboud, Hanna E. ; Gorin, Yves. / Redox dependence of glomerular epithelial cell hypertrophy in response to glucose. In: American Journal of Physiology - Renal Physiology. 2006 ; Vol. 290, No. 3.
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