Chronic lead intoxication causes a brain-specific nuclear protein to accumulate in the nuclei of cells lining kidney tubules.
A characteristic feature of chronic lead intoxication is the induction of intranuclear inclusion bodies in cells lining kidney proximal tubules. These are relatively insoluble lead- and protein-rich structures which may serve a protective function by sequestering lead. The most abundant protein of isolated inclusion bodies, p32/6.3, has been partially characterized by use of a monoclonal antibody. As predicted by biochemical analysis, p32/6.3 occurs in kidney only in conjunction with lead intoxication and inclusion body formation. It does not accumulate in other tissues as a result of lead exposure. Unexpectedly, p32/6.3 was found to be a constitutive protein of adult brain, occurring primarily in the cerebral cortex. Within this tissue, both neurons and astrocytes contained p32/6.3. The brain p32/6.3 was concentrated in the insoluble nuclear protein or matrix fraction, a localization reminiscent of the intranuclear inclusion bodies from lead-exposed kidney. Brain p32/6.3 was detected in rat, mouse, dog, man, and chicken. In rat brain, the appearance of p32/6.3 was developmentally regulated. Only traces were detected 3 days after birth but within 1-2 weeks adult levels were achieved. The presence in brain of a protein which is involved in a potentially protective response to lead suggests that the brain may also have such a protective mechanism.
D000367:Age Factors; D000818:Animals; D002467:Cell Nucleus / Q000032:analysis*; D002540:Cerebral Cortex / Q000032:analysis* / Q000254:growth & development; D002908:Chronic Disease; D005260:Female; D002479:Inclusion Bodies / Q000032:analysis; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D007854:Lead / Q000032:analysis; D007855:Lead Poisoning / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009419:Nerve Tissue Proteins / Q000032:analysis* / Q000502:physiology
D009419:Nerve Tissue Proteins; D007854:Lead