Urea-associated oxidative stress and Gadd153/CHOP induction

Zheng Zhang, Xiao Yan Yang, David M. Cohen

Research output: Contribution to journalArticlepeer-review

80 Scopus citations


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)
Pages (from-to)F786-F793
JournalAmerican Journal of Physiology - Renal Physiology
Issue number5 45-5
StatePublished - May 1999


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

ASJC Scopus subject areas

  • Physiology
  • Urology


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