A nuclear matrix protein stabilized by lead exposure: current knowledge and future prospects

p32/6.3, a low-abundance, highly conserved nuclear protein, is a target for lead. Very few low abundance nuclear proteins have been described and no others have been associated with lead. Its wide distribution and conservation indicate a fundamental nuclear role. Further, it increases many fold in grey matter of brain and spinal cord during the neonatal period; there are no other identified nuclear proteins which serve as markers for this period of nervous system development. There are several links between lead and p32/6.3. It is a major component of lead-induced intranuclear inclusion bodies from the kidney. Its accumulation in kidney is a relatively early event in the process of lead intoxication. Exposure to lead increases p32/6.3 in mouse neuroblastoma 2a cells within one day, blocking its degradation almost completely. These observations suggest that lead either structurally alters p32/6.3 or inhibits a protease for which p32/6.3 is a substrate. In these lead-treated cells nuclear envelope invaginations and small nuclear bodies increase. The possible involvement of lead and p32/6.3 with the formation and movement of nuclear bodies is discussed.