Neuronal death in the central nervous system demonstrates a non-fibrin substrate for plasmin.
Neuronal death in the central nervous system demonstrates a non-fibrin substrate for plasmin.
复制标题
中枢神经系统中的神经元死亡表明纤溶酶具有非纤维蛋白底物。
DOI：
10.1073/pnas.94.18.9779
复制
发表时间：
1997
影响因子：
11.1
通讯作者：
Strickland,S
中科院分区：
文献类型：
--
作者：
Tsirka,SE;Bugge,TH;Degen,JL;Strickland,S
缺乏纤溶酶原的小鼠表现出多种病理学，当动物也缺乏纤维蛋白（原）时，迄今为止检查的所有病理学都被逆转。这些结果表明，纤溶酶原的主要，也许是唯一的，生理作用是清除纤维蛋白。纤溶酶原缺乏的小鼠也显示出对兴奋性毒素诱导的神经变性的抵抗力，与敏感的野生型小鼠相反。基于纤溶酶原和纤维蛋白原之间的遗传相互作用，我们研究了纤溶酶原缺陷小鼠对神经细胞死亡的抵抗是否依赖于纤维蛋白（原）。出乎意料的是，缺乏纤溶酶原和纤维蛋白原的小鼠对神经退行性疾病的抵抗力达到了与纤溶酶原缺乏小鼠相当的水平。因此，纤溶酶在实验性神经元变性过程中作用于纤维蛋白以外的底物，并且在中枢神经系统的其他病理环境中可能具有类似的功能。
Mice deficient for plasminogen exhibit a variety of pathologies, all of which examined to date are reversed when the animals are also made fibrin(ogen) deficient. These results suggested that the predominant, and perhaps exclusive, physiological role of plasminogen is clearance of fibrin. Plasminogen-deficient mice also display resistance to excitotoxin-induced neurodegeneration, in contrast with wild-type mice, which are sensitive. Based on the genetic interaction between plasminogen and fibrinogen, we investigated whether resistance to neuronal cell death in the plasminogen-deficient mice is dependent on fibrin(ogen). Unexpectedly, mice lacking both plasminogen and fibrinogen are resistant to neurodegeneration to levels comparable to plasminogen-deficient mice. Therefore, plasmin acts on substrates other than fibrin during experimental neuronal degeneration, and may function similarly in other pathological settings in the central nervous system.