Selective activation in the MAPK pathway by Hg(II) in precision-cut rabbit renal cortical slices

Karen D. Turney, Alan R. Parrish, Jason Orozco, A. Jay Gandolfi

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

The kidneys are the primary organ for the accumulation and toxicity of inorganic mercury. In these studies the molecular response of precision-cut rabbit renal cortical slices to low levels of inorganic mercury was examined. Cortical slices (275 μm) were obtained from 1.0 kg NZW rabbits and exposed to mercuric chloride [Hg(II)] at concentrations of 0.01-10 μM for 2-8 h. Overt cytotoxicity, as assessed by intracellular K+ levels, was not observed following exposure to these concentrations of Hg(II). However, an induction of heme-oxygenase-1 (Hsp32) was seen following a 2-h challenge to Hg(II). A dose-dependent induction of the DNA binding activity of the AP-1 transcription factor after 4 h of Hg(II) exposure correlated with a dose- dependent enhancement of c-jun gene expression following 2 h of Hg(II) exposure. Additionally, an increase in phosphorylated c-Jun NH2-terminal protein kinase (JNK) was observed following 2 h of Hg(II) exposure. These results suggest activation of the mitogen-activated protein (MAP) signal transduction pathway, specifically the c-Jun NH2-terminal protein kinase (JNK) pathway. No changes were observed, however, in the DNA binding activity of ATF2 and Elk-1, transcription factors involved in both the JNK and p38 pathways of MAP signal transduction, nor in the gene expression of c-myc. This selectivity of alterations in molecular signaling suggests an acute response in signal transduction, specifically activation of the JNK pathway in renal tissue following exposure to nanomolar concentrations of Hg(II).

Original languageEnglish (US)
Pages (from-to)262-270
Number of pages9
JournalToxicology and Applied Pharmacology
Volume160
Issue number3
DOIs
StatePublished - Nov 1 1999

Keywords

  • AP-1
  • Inorganic mercury
  • JNK
  • Renal slices
  • c-jun

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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