INSERM U919, Serine Proteases and Pathophysiology of the Neurovascular Unit (SP2U), Cyceron, Caen Cedex F-14074, France.
Biol Cell. 2010 Aug 18;102(10):539-47. doi: 10.1042/BC20100072.
Despite its pro-fibrinolytic activity, tPA (tissue plasminogen activator) is a serine protease known to influence a number of physiological and pathological functions in the central nervous system. Accordingly, tPA was reported to mediate some of its functions in the central nervous system through NMDA (N-methyl-D-aspartate) receptors, LRP (low-density lipoprotein receptor-related protein) or annexin II.
We provide here both in vitro and in vivo evidence that tPA could mediate proteolysis and subsequent delocalization of neuronal nitric oxide synthase, thereby reducing endogenous neuronal nitric oxide release. We also demonstrate that although this effect is independent of NMDA receptors, LRP signalling and calpain-mediated proteolysis, it is dependent on the ability of tPA to promote the conversion of plasminogen into plasmin.
Altogether, these results demonstrate a new function for tPA in the central nervous system, which most likely contributes to its pleiotropic functions.
尽管组织型纤溶酶原激活物（tPA）具有纤维蛋白溶解活性，但它是一种丝氨酸蛋白酶，已知会影响中枢神经系统中的许多生理和病理功能。因此，据报道，tPA 通过 NMDA（N-甲基-D-天冬氨酸）受体、LRP（低密度脂蛋白受体相关蛋白）或膜联蛋白 II 来介导其在中枢神经系统中的一些功能。
我们在这里提供了体外和体内证据，表明 tPA 可以介导神经元型一氧化氮合酶的蛋白水解和随后的定位改变，从而减少内源性神经元一氧化氮的释放。我们还表明，尽管这种作用不依赖于 NMDA 受体、LRP 信号和钙蛋白酶介导的蛋白水解，但它依赖于 tPA 促进纤溶酶原转化为纤溶酶的能力。
总之，这些结果表明 tPA 在中枢神经系统中具有新的功能，这很可能与其多效性功能有关。
