Tucker H M, Kihiko-Ehmann M, Wright S, Rydel R E, Estus S
Department of Physiology, Sanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky, USA.
J Neurochem. 2000 Nov;75(5):2172-7. doi: 10.1046/j.1471-4159.2000.0752172.x.
Tissue plasminogen (plgn) activator (tPA) modulates neuronal death in models of stroke, excitotoxicity, and oxidative stress. Amyloid-beta (Abeta) appears central to Alzheimer's disease and is neurotoxic to neurons in vitro. Here, we evaluate tPA effects on Abeta toxicity. We report that tPA alone had no effect on Abeta toxicity. However, in combination with plgn, tPA reduced Abeta toxicity in a robust fashion. Moreover, the combined tPA and plgn treatment markedly inhibited Abeta accumulation. The addition of phenylmethylsulfonyl fluoride, a serine protease inhibitor, to a sample of tPA, plgn, and Abeta resulted in a marked reduction of Abeta degradation. We interpret the actions of tPA and plgn within the context of the ability of plasmin to degrade Abeta.
组织纤溶酶原（plgn）激活剂（tPA）在中风、兴奋性毒性和氧化应激模型中调节神经元死亡。β-淀粉样蛋白（Abeta）似乎是阿尔茨海默病的核心，并且在体外对神经元具有神经毒性。在此，我们评估tPA对Abeta毒性的影响。我们报告单独的tPA对Abeta毒性没有影响。然而，与plgn联合使用时，tPA以显著的方式降低了Abeta毒性。此外，tPA和plgn联合治疗显著抑制了Abeta的积累。向tPA、plgn和Abeta的样品中添加丝氨酸蛋白酶抑制剂苯甲基磺酰氟导致Abeta降解显著减少。我们在纤溶酶降解Abeta能力的背景下解释tPA和plgn的作用。
