Synthesis of urokinase-type plasminogen activator and of type-1 plasminogen activator inhibitor in neuronal cultures of human fetal brain: stimulation by phorbol ester.
Human neuronal brain cultures established from 12- and 14-week-old fetuses synthesize and secrete urokinase-type plasminogen activator (uPA) and limited amounts of tissue-type plasminogen activator (tPA). These cells also produce and secrete the endothelial cell-type PA inhibitor (PAI-1), which forms sodium dodecyl sulfate-stable tPA/PAI-1 complexes in the culture medium. Immunocytochemistry shows a predominant localization of uPA, tPA, and PAI-1 in neuronal cells, with only a very weak positivity detectable in the few glial cells present in these cultures. The protein kinase C (PKC) activator 12-O-tetradecanoylphorbol 13-acetate (TPA) stimulates the synthesis of both uPA and PAI-1, resulting in a final increase in the plasmin-generating capacity of neuronal cell cultures. No significant effect is observed, however, when cells are treated with the TPA analogue 4 alpha-phorbol 12,13-didecanoate, which is inactive as a PKC inducer, or with the neurotrophic polypeptide basic fibroblast growth factor. These data represent the first characterization of the plasmin-generating system in human fetal brain neurons and suggest a role for PKC in the modulation of uPA and PAI-1 synthesis.
Department of Biomedical Sciences and Biotechnologies, School of Medicine, University of Brescia, Italy.
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M
Presta
M G
MG
Ennas
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Torelli
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Ragnotti
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F
Gremo
D001921:Brain / Q000166:cytology / Q000201:enzymology*; D002478:Cells, Cultured; D005333:Fetus / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D009474:Neurons / Q000378:metabolism*; D010703:Phorbol Esters / Q000494:pharmacology*; D015849:Plasminogen Inactivators / Q000378:metabolism*; D014018:Tissue Distribution; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis*
D010703:Phorbol Esters; D015849:Plasminogen Inactivators; D014568:Urokinase-Type Plasminogen Activator