Alterations in rabbit kidney protein expression following lead exposure as analyzed by two-dimensional gel electrophoresis

Mary Helen Kanitz, Frank A. Witzmann, Huan Zhu, Carla D. Fultz, Steve Skaggs, William J. Moorman, Russell E. Savage

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

It was recently reported that low blood lead levels impaired kidneY- function in men. To develop a set of molecular markers of renal lead exposure and effect, we investigated changes in renal protein expression while approximating occupational lead exposure at subchronic, low blood levels. Lead was administered to male Dutch Belted rabbits as a lead acetate solution adjusted weekly to achieve and maintain the target blood lead levels of 0, 20, 40, and 80 μg/dL for 15 weeks. Lead exposure did not affect kidney or body weights. The effect of increasing blood lead on protein expression was evaluated in rabbit kidney by large-scale two-dimensional electrophoresis (2- DE). Significant quantitative changes (p < 0.05) occurred in a dose-related manner in 12 proteins at 20 μg/dL exposure, 25 at 40 μg/dL, and 102 at 80 μg/dL. At a higher level of significance (p < 0.001), 40 μg/dL blood lead resulted in one protein alteration and 80 μg/dL affected 14 proteins. A set of quantitatively altered charge variants was tentatively identified as glutathione-S-transferase (GST), based on similar observations in rodents subjected to short-term, very high lead exposure. The significance of the protein alterations observed as markers of toxicity awaits their conclusive identification. Investigation of the kidney 2-DE profile in lead-exposed rabbit may be useful in understanding the mechanism of lead nephrotoxicity in humans.

Original languageEnglish (US)
Pages (from-to)2977-2985
Number of pages9
JournalELECTROPHORESIS
Volume20
Issue number14
DOIs
StatePublished - Nov 17 1999

Keywords

  • Lead toxicity
  • Rabbit kidney
  • Two-dimensional polyacrylamide gel electrophoresis

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Clinical Biochemistry

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