Blömer U, Kafri T, Randolph-Moore L, Verma I M, Gage F H
Laboratory of Genetics, The Salk Institute, La Jolla, CA 92037, USA.
Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2603-8. doi: 10.1073/pnas.95.5.2603.
Bcl-xL suppresses apoptotic cell death induced by diverse stimuli in cell lines in vitro. To examine the mechanism by which axotomized cholinergic neurons die in vivo, lentiviral vectors expressing Bcl-xL, human nerve growth factor (hNGF), or green fluorescent protein were injected into the septum 3 weeks before transection of the fimbria fornix. Three weeks after transection, Bcl-xL- and hNGF-injected animals showed significantly higher numbers of spared cholinergic neurons compared with control (green fluorescent protein) injected animals. These results provide evidence that adult axotomized cholinergic neurons die of apoptotic death that can be prevented by local delivery of hNGF or intracellular delivery of Bcl-xL.
Bcl-xL在体外细胞系中可抑制多种刺激诱导的凋亡性细胞死亡。为研究体内切断轴突的胆碱能神经元死亡的机制，在穹窿海马伞横断前3周，将表达Bcl-xL、人神经生长因子（hNGF）或绿色荧光蛋白的慢病毒载体注入隔区。横断后3周，与注射对照（绿色荧光蛋白）的动物相比，注射Bcl-xL和hNGF的动物中 spared胆碱能神经元数量显著增多。这些结果证明，成年期切断轴突的胆碱能神经元死于凋亡性死亡，而局部递送hNGF或细胞内递送Bcl-xL可预防这种死亡。
