Regional protein alterations in rat kidneys induced by lead exposure

Frank A. Witzmann, Carla D. Fultz, Raymond A. Grant, Linda S. Wright, Steven E. Kornguth, Frank L. Siegel

Research output: Chapter in Book/Report/Conference proceedingChapter


Lead is a potent neuro- and nephrotoxin in humans and a renal carcinogen in rats. Previous studies have detected lead-induced increases in the activities of specific detoxification enzymes in distinct kidney cell types preceding irreversible renal damage. While preferential susceptibility of the highly vascularized cortex to the effects of lead is clear, lead effects on the medullary region have remained unexplored. The present study was undertaken to investigate the extent to which regional renal protein expression differs and to determine which, if any, regionally distinct protein markers indicative of lead's renotoxic mechanism might be detected in kidney cortical and medullary cytosols. We examined protein expression in these two functionally and anatomically distinct regions, and identified several proteins that are differentially expressed in those regions and were significantly altered by lead. Kidney cytosols from rats injected with lead acetate (114 mg/kg, three consecutive daily injections) were separated by two-dimensional electrophoresis. Lead exposure significantly (P<0.001) altered the abundance (either ↑ or ↓) of 76 proteins in the cortex and only 13 in the medulla. Eleven of the proteins altered in the protein patterns were conclusively identified either by matrix-assisted laser desorption/ionization mass spectrometry / electrospray ionization-mass spectrometry (MALDI-MS/ESI-MS) analysis of peptide digests, immunological methods, or by gel matching. Several of the cortical proteins altered by lead were unchanged in the medulla while others underwent similar but lesser alterations. These observations reflect the complexity of lead's nephrotoxicity and endorse the application of proteomics in mechanistic studies as well as biomarker development in a variety of toxicologic paradigms.

Original languageEnglish (US)
Title of host publicationFrom Genome to Proteome: Advances in the Practice & Application of Proteomics
Number of pages9
ISBN (Electronic)9783527613489
ISBN (Print)9783527301546
StatePublished - Dec 26 2007


  • Cortex
  • Cytoplasm
  • Kidney
  • Lead
  • Medulla
  • Proteomics
  • Rat
  • Two-dimensional electrophoresis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Witzmann, F. A., Fultz, C. D., Grant, R. A., Wright, L. S., Kornguth, S. E., & Siegel, F. L. (2007). Regional protein alterations in rat kidneys induced by lead exposure. In From Genome to Proteome: Advances in the Practice & Application of Proteomics (pp. 363-371). Wiley-Blackwell.