Houenou L J, Turner P L, Li L, Oppenheim R W, Festoff B W
Department of Neurobiology and Anatomy, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC 27157.
Proc Natl Acad Sci U S A. 1995 Jan 31;92(3):895-9. doi: 10.1073/pnas.92.3.895.
Protease nexin I (PNI) is a member of the family of serine protease inhibitors (serpins) that have been shown to promote neurite outgrowth in vitro from different neuronal cell types. These include neuroblastoma cells, hippocampal neurons, and sympathetic neurons. Free PNI protein is markedly decreased in various anatomical brain regions, including hippocampus, of patients with Alzheimer disease. Here, we report that PNI rescued spinal motoneurons during the period of naturally occurring (programmed) cell death in the chicken in a dose-dependent fashion. Furthermore, PNI prevented axotomy-induced spinal motoneuron death in the neonatal mouse. The survival effect of PNI on motoneurons during the period of programmed cell death was not associated with increased intramuscular nerve branching. PNI also significantly increased the nuclear size of motoneurons during the period of programmed cell death and prevented axotomy-induced atrophy of surviving motoneurons. These results are consistent with the possible role of PNI as a neurotrophic agent. They also support the idea that serine proteases or, more precisely, the balance of proteases and serpins may be involved in regulating the fate of neuronal cells during development.
蛋白酶抑制剂I（PNI）是丝氨酸蛋白酶抑制剂（丝氨酸蛋白酶抑制剂家族）家族的成员，已被证明在体外能促进不同类型神经元细胞的神经突生长。这些细胞包括神经母细胞瘤细胞、海马神经元和交感神经元。在阿尔茨海默病患者的包括海马体在内的各个脑区中，游离PNI蛋白明显减少。在此，我们报告PNI在鸡自然发生（程序性）细胞死亡期间以剂量依赖的方式拯救脊髓运动神经元。此外，PNI可防止新生小鼠轴突切断诱导的脊髓运动神经元死亡。PNI在程序性细胞死亡期间对运动神经元的存活作用与肌肉内神经分支增加无关。PNI还在程序性细胞死亡期间显著增加运动神经元的核大小，并防止轴突切断诱导的存活运动神经元萎缩。这些结果与PNI作为神经营养因子的可能作用一致。它们还支持丝氨酸蛋白酶或者更确切地说，蛋白酶和丝氨酸蛋白酶抑制剂的平衡可能参与调节发育过程中神经元细胞命运的观点。
