PMID- 10215917 OWN - NLM STAT- MEDLINE DCOM- 19990526 LR - 20231213 IS - 0953-816X (Print) IS - 0953-816X (Linking) VI - 11 IP - 5 DP - 1999 May TI - BDNF stimulates expression, activity and release of tissue-type plasminogen activator in mouse cortical neurons. PG - 1639-46 AB - Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor involved in neuronal development and synaptic plasticity. Although the physiological effects of BDNF have been examined in detail, target proteins which mediate its actions remain largely unknown. Here, we report that BDNF stimulates the expression of tissue-type plasminogen activator (tPA) in primary cultures of cortical neurons in a time- and concentration-dependent manner. Among the other members of the neurotrophin family, neurotrophin-4 (NT-4) and to a lesser extent neurotrophin-3 (NT-3) also increased tPA mRNA expression, while nerve growth factor (NGF) was devoid of any effect. Induction of tPA expression by BDNF is accompanied by an increase in the proteolytic activity of tPA associated with cortical neurons and a release of tPA into the extracellular space. Release of tPA induced by BDNF depends on extracellular Ca2+ since it is markedly reduced in the presence of ethylene glycol-bis(beta-aminoethylether)-N,N,N',N'-tetraacetic acid (EGTA). Up-regulation of tPA expression by BDNF is followed by the induction of plasminogen activator inhibitor 2 (PAI-2), an inhibitor of tPA. Together these results suggest that activation of tPA by BDNF may contribute to structural changes associated with neuronal development or synaptic plasticity. FAU - Fiumelli, H AU - Fiumelli H AD - Laboratoire de Recherche Neurologique, Institut de Physiologie et Service de Neurologie du CHUV, Faculte de Medecine, Universite de Lausanne, Switzerland. FAU - Jabaudon, D AU - Jabaudon D FAU - Magistretti, P J AU - Magistretti PJ FAU - Martin, J L AU - Martin JL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - France TA - Eur J Neurosci JT - The European journal of neuroscience JID - 8918110 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Chelating Agents) RN - 0 (DNA Primers) RN - 0 (Nerve Growth Factors) RN - 0 (Neuropeptides) RN - 0 (Neurotrophin 3) RN - 0 (Plasminogen Activator Inhibitor 1) RN - 0 (Plasminogen Activator Inhibitor 2) RN - 0 (Protein Synthesis Inhibitors) RN - 0 (RNA, Messenger) RN - 0 (Serine Proteinase Inhibitors) RN - 0 (Serpins) RN - 1CC1JFE158 (Dactinomycin) RN - 526U7A2651 (Egtazic Acid) RN - 66-40-0 (Tetraethylammonium) RN - 98600C0908 (Cycloheximide) RN - P658DCA9XD (neurotrophin 4) RN - RWP5GA015D (Potassium) SB - IM MH - Animals MH - Blotting, Northern MH - Brain-Derived Neurotrophic Factor/*pharmacology MH - Cells, Cultured MH - Cerebral Cortex/chemistry/cytology/physiology MH - Chelating Agents/pharmacology MH - Cycloheximide/pharmacology MH - DNA Primers MH - Dactinomycin/pharmacology MH - Egtazic Acid/pharmacology MH - Gene Expression/physiology MH - Mice MH - Nerve Growth Factors/pharmacology MH - Neuronal Plasticity/*physiology MH - Neurons/chemistry/drug effects/*physiology MH - Neuropeptides/genetics MH - Neurotrophin 3 MH - Plasminogen Activator Inhibitor 1/*genetics MH - Plasminogen Activator Inhibitor 2/*genetics MH - Potassium/pharmacology MH - Protein Synthesis Inhibitors/pharmacology MH - RNA, Messenger/analysis MH - Serine Proteinase Inhibitors/genetics MH - Serpins/genetics MH - Tetraethylammonium/pharmacology MH - Neuroserpin EDAT- 1999/04/24 00:00 MHDA- 1999/04/24 00:01 CRDT- 1999/04/24 00:00 PHST- 1999/04/24 00:00 [pubmed] PHST- 1999/04/24 00:01 [medline] PHST- 1999/04/24 00:00 [entrez] AID - 10.1046/j.1460-9568.1999.00580.x [doi] PST - ppublish SO - Eur J Neurosci. 1999 May;11(5):1639-46. doi: 10.1046/j.1460-9568.1999.00580.x.