Expression of nerve growth factor-induced type 1 plasminogen activator inhibitor (PAI-1) mRNA is inhibited by genistein and wortmannin.
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 microM. Wortmannin, a potent and specific inhibitor of phosphatidylinositol 3-kinase (PI-3 kinase), decreased induction of PAI-1 mRNA level at doses of > or = 10(-7) M.
Takahashi
H
H
Department of Biochemistry, School of Medicine, Nihon University, Tokyo, Japan.
Uno
S
S
Watanabe
Y
Y
Arakawa
K
K
Nakagawa
S
S
D000730:Androstadienes / Q000494:pharmacology*; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D019833:Genistein / Q000494:pharmacology*; D020932:Nerve Growth Factor / Q000378:metabolism* / Q000494:pharmacology*; D016716:PC12 Cells; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D000077191:Wortmannin
D000730:Androstadienes; D004791:Enzyme Inhibitors; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D020932:Nerve Growth Factor; D019833:Genistein; D000077191:Wortmannin