Expression of nerve growth factor-induced type I plasminogen activator inhibitor (PAI-I) mRNA is inhibited by genistein and wortmannin

Nerve growth factor (NGF), which acts as a neurotrophic factor in a rat phe ochromocytoma fell line (PC12), stimulated type 1 plasminogen activator inh ibitor (PAI-1) mRNA expression from 1 to 5 h, after addition at 5 ng/ml. PA I-1 antigen in culture medium, which was measured using an enzyme linked im munosorbent assay (ELISA), was also increased dose dependently by the addit ion of NGF. Neither epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), phorbol myristate acetate (PMA) nor forskolin increased PAI- 1 mRNA expression in PC12 cells. Genistein, an inhibitor of tyrosine protei n kinase, completely inhibited NGF induced PAI-1 mRNA in the presence of 10 0 mu M Wortmannin, a potent and specific inhibitor of phosphatidylinositol 3-kinase (PI-3 kinase), decreased induction of PAI-1 mRNA level at doses of greater than or equal to 10(-7) M. NeuroReport 11:1111-1115 (C) 2000 Lippi ncott Williams & Wilkins.