A lead-associated nuclear protein which increases in maturing brain and in differentiating neuroblastoma 2A cells exposed to cyclic AMP-elevating agents.

The lead-associated nuclear protein, p32/6.3, increases significantly in the postnatally developing rat cerebral cortex (Egle and Shelton, J. Biol. Chem., 261 (1986) 2294-2298). In the present study, this increase has been identified with late development of the cerebral cortex or forebrain because p32/6.3 reached adult levels 10 to 14 days after birth in guinea pig (a precocial animal) and after hatching in chicken. Comparison with other developmental processes indicates that p32/6.3 reaches adult levels just before or during the period of synapse maturation. Thus p32/6.3 may prove useful as a biochemical indicator of nuclear maturation in this period. The developmental regulation of p32/6.3 was further studied in mouse neuroblastoma 2a (Nb2a) cells. In vitro induction of differentiation of Nb2a cells by serum withdrawal from the culture medium increased p32/6.3, implicating p32/6.3 with differentiating neurons. This association was further strengthened when treatment of the Nb2a cells for 24 h with dibutyryl cAMP (1-5 mM), papaverine (5-12.5 micrograms/ml) or 3-isobutyl-1-methylxanthine (IBMX; 50-250 microM) increased the abundance of p32/6.3 1.5- to 3-fold more than serum withdrawal alone. 8-Bromo-cAMP (2-4 mM), N6-benzoyl cAMP (4 mM) and forskolin (10 microM) also increased the abundance of p32/6.3 in Nb2a cells, arguing that cAMP is involved in p32/6.3 regulation. These results, in conjunction with the postnatal increase of p32/6.3 in cerebral cortex, suggest a relationship between p32/6.3 levels and neuronal maturation.