SYNTHESIS OF UROKINASE-TYPE PLASMINOGEN-ACTIVATOR AND OF TYPE-1 PLASMINOGEN-ACTIVATOR INHIBITOR IN NEURONAL CULTURES OF HUMAN FETAL BRAIN - STIMULATION BY PHORBOL ESTER

Abstract: 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 (PAII), which forms sodium dodecyl sulfate‐stable tPA/PAI‐I 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 12‐0‐tetradecanoylphorbol 13‐ac‐etate (TPA) stimulates the synthesis of both uPA and PAI‐I, 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 4a‐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‐I synthesis. Copyright © 1990, Wiley Blackwell. All rights reserved