MEMBRANE BIOPHYSICS AND BIOCHEMISTRYExpression of nerve growth factor-induced type 1 plasminogen activator inhibitor (PAI-1) mRNA is inhibited by genistein and wortmanninTakahashi, Hideo1,2; Uno, Shigeyuki1; Watanabe, Yoshifumi1; Arakawa, Kazuo1; Nakagawa, Shigeki1Author Information 1Department of Biochemistry, School of Medicine, Nihon University, Ohyaguchi-kami-machi, Itabashi-ku, Tokyo 173–8610, Japan 2Corresponding Author: Hideo Takahashi Received 14 December 1999; accepted 30 January 2000 NeuroReport: April 7, 2000 - Volume 11 - Issue 5 - p 1111-1115 Buy Abstract Nerve growth factor (NGF), which acts as a neurotrophic factor in a rat pheochromocytoma cell line (PC12), stimulated type 1 plasminogen activator inhibitor (PAI-1) mRNA expression from 1 to 5 h, after addition at 5 ng/ml. PAI-1 antigen in culture medium, which was measured using an enzyme linked immunosorbent assay (ELISA), was also increased dose dependently by the addition 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 protein kinase, completely inhibited NGF induced PAI-1 mRNA in the presence of 100 μM. Wortmannin, a potent and specific inhibitor of phosphatidylinositol 3-kinase (PI-3 kinase), decreased induction of PAI-1 mRNA level at doses of ≥ 10-7 M. © 2000 Lippincott Williams & Wilkins, Inc.