Urea and hypertonicity increase expression of heme oxygenase-1 in murine renal medullary cells

W. Tian, H. L. Bonkovsky, S. Shibahara, D. M. Cohen

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Epithelial cells derived from the mammalian kidney medulla are responsive to urea at the levels of signal transduction and gene regulation. Hybridization of RNA harvested from control- and urea-treated murine inner medullary collecting duct (mIMCD3) cells with a cDNA expression array encoding stress-responsive genes suggested that heme oxygenase (HO)-1 mRNA was upregulated by urea. RNase protection assay confirmed this upregulation; hypertonicity also increased HO-1 mRNA expression but neither hypertonic NaCl nor urea were effective in the nonrenal 3T3 cell line. The effect on HO-1 expression appeared to be transcriptionally mediated on the basis of mRNA half-life studies and reporter gene analyses using the promoters of both human and chicken HO-1. Although urea signaling resembles that of heavy metal signaling in other contexts, the effect of urea on HO-1 transcription was independent of the cadmium response element in this promoter. Urea-inducible HO-1 expression was sensitive to antioxidants but not to scavengers of nitric oxide. Urea also upregulated HO-1 protein expression and pharmacological inhibition of HO-1 action with zinc protoporphyrin-sensitized mlMCD3 cells to the adverse effects of hypertonicity but not to urea. Coupled with the prior observation of others that HO-1 expression increases along the renal corticomedullary gradient, these data suggest that HO-1 expression may comprise an element of the adaptive response to hypertonicity and/or urea in renal epithelial cells.

Original languageEnglish (US)
Pages (from-to)F983-F991
JournalAmerican Journal of Physiology - Renal Physiology
Volume281
Issue number5 50-5
DOIs
StatePublished - 2001

Keywords

  • Osmotic
  • Oxidative stress
  • Sodium chloride
  • Transcription

ASJC Scopus subject areas

  • Physiology
  • Urology

Fingerprint Dive into the research topics of 'Urea and hypertonicity increase expression of heme oxygenase-1 in murine renal medullary cells'. Together they form a unique fingerprint.

  • Cite this