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

It was recently reported that low blood lead levels impaired kidney functio n in men. To develop a set of molecular markers of renal lead exposure and effect, we investigated changes in renal protein expression while approxima ting occupational lead exposure at subchronic, low blood levels. Lead was a dministered to male Dutch Belted rabbits as a lead acetate solution adjuste d weekly to achieve and maintain the target blood lead levels of 0, 20, 40, and 80 mu g/dL for 15 weeks. Lead exposure did not affect kidney or body w eights. The effect of increasing blood lead on protein expression was evalu ated in rabbit kidney by large-scale two-dimensional electrophoresis (2-DE) . Significant quantitative changes (p < 0.05) occurred in a dose-related ma nner in 12 proteins at 20 mu g/dL exposure, 25 at 40 mu g/dL, and 102 at 80 mu g/dL. At a higher level of significance (p < 0.001), 40 mu g/dL blood l ead resulted in one protein alteration and 80 mu g/dL affected 14 proteins. A set of quantitatively altered charge variants was tentatively identified as glutathione-S-transferase (GST), based on similar observations in roden ts subjected to short-term, very high lead exposure. The significance of th e protein alterations observed as markers of toxicity awaits their conclusi ve identification. Investigation of the kidney 2-DE profile in lead-exposed rabbit may be useful in understanding the mechanism of lead nephrotoxicity in humans.