The clinical effects of lead intoxication are well known, but there is increasing concern over the possible effects of low level lead exposure. This proposal is directed at a nuclear protein which is a target for ingested lead. The protein, p32/6.3, is an abundant component of lead- induced intranuclear inclusion bodies in kidney. In normal adults it is most abundant in central nervous system neurons, the increase occurring as synapses mature. The long term objectives are to understand lead's effects on p32/6.3 in brain as well as in kidney and other cells where it is normally a low-abundance component, and further, to understand the consequences of these effects. A monoclonal antibody will be used to assay p32/6.3 pool size in several lead exposed models: cultured brain microvessel endothelial cells; cerebrum, cerebellum, brain microvessels, and kidney of adults and of neonates whose mothers are lead exposed; and kidney of adults after EDTA chelation therapy. Using information from a partial peptide sequence, the polymerase chain reaction and cDNA cloning will be used to complete the sequence; this may confirm homology with a cAMP-binding protein. Using cDNA sequence, fusion proteins will be used as antigens; the resultant antibodies will be used to perform immunocytochemistry in the models described above. A related project will study the mechanism of induction of a lead-induced protein.
