Fiumelli H, Jabaudon D, Magistretti P J, Martin J L
Laboratoire de Recherche Neurologique, Institut de Physiologie et Service de Neurologie du CHUV, Faculté de Médecine, Université de Lausanne, Switzerland.
Eur J Neurosci. 1999 May;11(5):1639-46. doi: 10.1046/j.1460-9568.1999.00580.x.
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.
脑源性神经营养因子（BDNF）是一种参与神经元发育和突触可塑性的神经营养因子。尽管BDNF的生理作用已得到详细研究，但其介导作用的靶蛋白仍大多未知。在此，我们报告BDNF以时间和浓度依赖性方式刺激皮质神经元原代培养物中组织型纤溶酶原激活物（tPA）的表达。在神经营养因子家族的其他成员中，神经营养因子-4（NT-4）以及程度较轻的神经营养因子-3（NT-3）也增加了tPA mRNA的表达，而神经生长因子（NGF）则没有任何作用。BDNF诱导tPA表达的同时，与皮质神经元相关的tPA蛋白水解活性增加，且tPA释放到细胞外空间。BDNF诱导的tPA释放依赖于细胞外Ca2+，因为在乙二醇双（β-氨基乙基醚）-N，N，N'，N'-四乙酸（EGTA）存在时其明显减少。BDNF上调tPA表达后会诱导纤溶酶原激活物抑制剂2（PAI-2），即tPA的一种抑制剂。这些结果共同表明，BDNF激活tPA可能有助于与神经元发育或突触可塑性相关的结构变化。
