Urea-associated oxidative stress and Gadd153/CHOP induction

Zheng Zhang, Xiao Yan Yang, David Cohen

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

Urea treatment (100-300 mM) increased expression of the oxidative stress-responsive transcription factor, Gadd153/CHOP, at the mRNA and protein levels (at ≥4 h) in renal medullary mIMCD3 cells in culture, whereas other solutes did not. Expression of the related protein, CCAAT/enhancer-binding protein (C/EBP-β), was not affected, nor was expression of the sensor of endoplasmic reticulum stress, grp78. Urea modestly increased Gadd153 transcription by reporter gene analysis but failed to influence Gadd153 mRNA stability. Importantly, upregulation of Gadd153 mRNA and protein expression by urea was antioxidant sensitive. Accordingly, urea treatment was associated with oxidative stress, as quantitated by intracellular reduced glutathione content in mIMCD3 cells. In addition, antioxidant treatment partially inhibited the ability of urea to activate transcription of an Egr-1 luciferase reporter gene. Therefore oxidative stress represents a novel solute-signaling pathway in the kidney medulla and, potentially, in other tissues.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Renal Physiology
Volume276
Issue number5 45-5
StatePublished - May 1999

Fingerprint

Urea
Oxidative Stress
Reporter Genes
Antioxidants
Transcription Factor CHOP
Kidney Medulla
CCAAT-Enhancer-Binding Proteins
Messenger RNA
Proteins
Endoplasmic Reticulum Stress
RNA Stability
Protein C
Luciferases
Glutathione
Up-Regulation
Cell Culture Techniques
Kidney

Keywords

  • Cell culture
  • Egr-1
  • Hypertonic
  • Kidney
  • Mouse
  • Sodium chloride

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Urea-associated oxidative stress and Gadd153/CHOP induction. / Zhang, Zheng; Yang, Xiao Yan; Cohen, David.

In: American Journal of Physiology - Renal Physiology, Vol. 276, No. 5 45-5, 05.1999.

Research output: Contribution to journalArticle

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AB - Urea treatment (100-300 mM) increased expression of the oxidative stress-responsive transcription factor, Gadd153/CHOP, at the mRNA and protein levels (at ≥4 h) in renal medullary mIMCD3 cells in culture, whereas other solutes did not. Expression of the related protein, CCAAT/enhancer-binding protein (C/EBP-β), was not affected, nor was expression of the sensor of endoplasmic reticulum stress, grp78. Urea modestly increased Gadd153 transcription by reporter gene analysis but failed to influence Gadd153 mRNA stability. Importantly, upregulation of Gadd153 mRNA and protein expression by urea was antioxidant sensitive. Accordingly, urea treatment was associated with oxidative stress, as quantitated by intracellular reduced glutathione content in mIMCD3 cells. In addition, antioxidant treatment partially inhibited the ability of urea to activate transcription of an Egr-1 luciferase reporter gene. Therefore oxidative stress represents a novel solute-signaling pathway in the kidney medulla and, potentially, in other tissues.

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