Inhibition of nerve growth factor-induced B-50/GAP-43 expression by antisense oligomers interferes with neurite outgrowth of PC12 cells.

Substantial evidence has now been gathered for the involvement of B-50/GAP-43 in neuronal development and regeneration. The precise role of this protein, however, is still debated. In an earlier study, a linear correlation between NGF-induced neurite outgrowth and B-50/GAP-43 levels was observed in PC12 cells. To establish the involvement of B-50/GAP-43 expression in neurite outgrowth in these cells, we interfered with the expression by antisense oligomers and measured the outgrowth. In the present study, a B-50/GAP-43 antisense 5'-oligomer interfered both with the NGF-induced increase in B-50/GAP-43 and with neurite outgrowth, whereas an antisense 3'-oligomer was ineffective. We conclude, that in PC12 cells under normal conditions B-50/GAP-43 expression and neurite outgrowth are or become coupled upon NGF-induction, in contrast to the situation in PC12 clones with no or very low B-50/GAP-43 expression.