Bcl-xL可保护成年隔区胆碱能神经元免受轴突切断所致的细胞死亡。
Bcl-xL protects adult septal cholinergic neurons from axotomized cell death.
作者信息
Blömer U, Kafri T, Randolph-Moore L, Verma I M, Gage F H
机构信息
Laboratory of Genetics, The Salk Institute, La Jolla, CA 92037, USA.
出版信息
Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2603-8. doi: 10.1073/pnas.95.5.2603.
Abstract
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.
摘要
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。
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本文引用的文献
1
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Proc Natl Acad Sci U S A. 1997 Sep 16;94(19):10319-23. doi: 10.1073/pnas.94.19.10319.
2
Highly efficient and sustained gene transfer in adult neurons with a lentivirus vector.利用慢病毒载体在成年神经元中实现高效且持续的基因转移。
J Virol. 1997 Sep;71(9):6641-9. doi: 10.1128/JVI.71.9.6641-6649.1997.
3
4
Nedd2 is required for apoptosis after trophic factor withdrawal, but not superoxide dismutase (SOD1) downregulation, in sympathetic neurons and PC12 cells.在交感神经元和PC12细胞中，营养因子撤除后诱导细胞凋亡需要Nedd2，但超氧化物歧化酶（SOD1）下调则不需要Nedd2。
J Neurosci. 1997 Mar 15;17(6):1911-8. doi: 10.1523/JNEUROSCI.17-06-01911.1997.
5
Bcl-x(L) forms an ion channel in synthetic lipid membranes.Bcl-x(L)在合成脂质膜中形成离子通道。
Nature. 1997 Jan 23;385(6614):353-7. doi: 10.1038/385353a0.
6
Expression of interleukin-1 beta converting enzyme gene family and bcl-2 gene family in the rat brain following permanent occlusion of the middle cerebral artery.大脑中动脉永久性闭塞后大鼠脑中白细胞介素-1β转化酶基因家族和bcl-2基因家族的表达
J Cereb Blood Flow Metab. 1997 Jan;17(1):11-8. doi: 10.1097/00004647-199701000-00003.
7
Efficient transfer, integration, and sustained long-term expression of the transgene in adult rat brains injected with a lentiviral vector.在注射慢病毒载体的成年大鼠脑中，转基因的高效转移、整合及长期持续表达。
Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):11382-8. doi: 10.1073/pnas.93.21.11382.
8
Apoptosis of bcl-x-deficient telencephalic cells in vitro.体外培养的bcl-x基因缺陷型端脑细胞凋亡
J Neurosci. 1996 Mar 1;16(5):1753-8. doi: 10.1523/JNEUROSCI.16-05-01753.1996.
9
The pCL vector system: rapid production of helper-free, high-titer, recombinant retroviruses.pCL载体系统：快速生产无辅助病毒、高滴度的重组逆转录病毒。
J Virol. 1996 Aug;70(8):5701-5. doi: 10.1128/JVI.70.8.5701-5705.1996.
10
Inactivation of bcl-2 results in progressive degeneration of motoneurons, sympathetic and sensory neurons during early postnatal development.bcl-2的失活会导致出生后早期发育过程中运动神经元、交感神经元和感觉神经元的进行性退化。
Neuron. 1996 Jul;17(1):75-89. doi: 10.1016/s0896-6273(00)80282-2.
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