Nerve Growth Factor Signaling through p75 Induces Apoptosis in Schwann Cells via a Bcl-2-Independent Pathway
Nerve Growth Factor Signaling through p75 Induces Apoptosis in Schwann Cells via a Bcl-2-Independent Pathway
复制标题
通过 p75 的神经生长因子信号传导通过 Bcl-2 独立途径诱导雪旺细胞凋亡
DOI：
--
复制
发表时间：
1999
影响因子：
5.3
通讯作者：
T. Kilpatrick
中科院分区：
文献类型：
--
作者：
M. Soilu;P. Ekert;T. Bucci;D. Syroid;P. Bartlett;T. Kilpatrick
在正常发育过程中和轴突损伤后，细胞凋亡参与雪旺细胞数量的调节，但雪旺细胞死亡的分子调节仍然未知。我们已经使用稳定转染的大鼠雪旺细胞系研究神经生长因子（NGF），抗凋亡蛋白Bcl-2和细胞因子反应调节剂A（CrmA）在体外调节雪旺细胞死亡的潜在作用。Bcl-2可抑制存活因子撤除诱导的雪旺细胞凋亡，而CrmA则无此作用。与此相反，Bcl-2转染的雪旺细胞对外源性神经生长因子诱导的细胞凋亡敏感，而CrmA表达细胞系则具有抗性。在Bcl-2转染的细胞系上，低亲和力神经营养因子受体p75而不是高亲和力TrkA受体的高水平的证明表明，NGF诱导的杀伤是由p75介导的。从p75敲除小鼠分离的雪旺细胞对NGF诱导的细胞死亡的抗性证实了这一点。神经生长因子也促进野生型小鼠和大鼠雪旺细胞的死亡，在生存因子撤出的情况下。内源性Bcl-2 mRNA表达的野生型雪旺细胞在所有条件下，促进生存，但下调至不可检测的水平后，生存因子撤出。总之，我们的研究结果表明，存在两个独立的途径，加快雪旺细胞凋亡：Bcl-2阻断途径启动的营养支持的损失，和Bcl-2的独立，CrmA阻断途径介导的p75受体。
Apoptosis is involved in the regulation of Schwann cell numbers during normal development and after axonal damage, but the molecular regulation of Schwann cell death remains unknown. We have used stably transfected rat Schwann cell lines to study the potential roles of nerve growth factor (NGF), the antiapoptotic protein Bcl-2 and the cytokine response modifier A (CrmA) in modulating Schwann cell death in vitro. Bcl-2 inhibited Schwann cell apoptosis induced by survival factor withdrawal, whereas CrmA did not. In contrast, Bcl-2-transfected Schwann cells were susceptible to apoptosis in response to exogenous NGF, whereas CrmA-expressing cell lines were resistant. Demonstration of high levels of the low-affinity neurotrophin receptor p75 but not the high-affinity TrkA receptor on the Bcl-2-transfected cell lines suggested that the NGF-induced killing was mediated by p75. This was confirmed by resistance of Schwann cells isolated from p75 knockout mice to the NGF-induced cell death. Nerve growth factor also promoted the death of wild-type mouse and rat Schwann cells in the absence of survival factor withdrawal. Endogenous Bcl-2 mRNA was expressed by wild-type Schwann cells in all conditions that promoted survival but was downregulated to undetectable levels after survival factor withdrawal. In conclusion, our results demonstrate the existence of two separate pathways that expedite apoptosis in Schwann cells: a Bcl-2-blockable pathway initiated on loss of trophic support, and a Bcl-2-independent, CrmA-blockable pathway mediated via the p75 receptor.
影响因子：
56.9
作者：
Wang, CY;Mayo, MW;Baldwin, AS
通讯作者：
Baldwin, AS
影响因子：
56.9
作者：
RABIZADEH, S;OH, J;BREDESEN, DE
通讯作者：
BREDESEN, DE
DOI：
10.1073/pnas.84.23.8735
发表时间：
1987-12-01
影响因子：
11.1
作者：
HEUMANN, R;LINDHOLM, D;THOENEN, H
通讯作者：
THOENEN, H