Leukemia Inhibitory Factor Requires Concurrent p75LNTR Signaling to Induce Apoptosis of Cultured Sympathetic Neurons
Leukemia Inhibitory Factor Requires Concurrent p75LNTR Signaling to Induce Apoptosis of Cultured Sympathetic Neurons
复制标题
白血病抑制因子需要同时 p75LNTR 信号传导来诱导培养的交感神经元凋亡
DOI：
10.1523/jneurosci.20-11-04198.2000
复制
发表时间：
2000
期刊：
影响因子：
--
通讯作者：
J. Kessler
中科院分区：
文献类型：
--
作者：
S. Savitz;J. Kessler
细胞凋亡可能是由于配体与质膜受体结合引起的阳性诱导或由于抑制信号丢失引起的阴性诱导。例如，通过暴露于白血病抑制因子（LIF）或通过剥夺神经生长因子，可以在培养物中诱导发育中的交感神经元的凋亡。本研究比较了这两种不同刺激激活交感神经元的细胞死亡途径。这两种类型的细胞死亡发育调节，都是最大的，在出生后立即和消失在未来2周。这两种类型的细胞死亡减少基因缺失的Bax或通过病毒介导的Bcl-2的过表达。类似地，通过抑制半胱天冬酶活性或通过用反义寡核苷酸抑制Nedd-2合成，两者都降低。最后，两者都涉及c-Jun N-末端激酶（JNK）信号传导的激活。交感神经元的Nedd-2表达与LIF介导的细胞死亡的发育损失平行下降，这表明在发育过程中caspase的下调可能是精氨酸介导的细胞凋亡损失的基础。用阻断低亲和力神经营养因子受体（p75 LNTR）功能的抗体治疗交感神经元可防止LIF诱导的细胞死亡。类似地，p75 LNTR的基因缺失阻止了LIF处理后的细胞凋亡。这些观察结果表明，并发p75 LNTR信号转导是必要的LIF诱导的细胞死亡，并表明甜菜碱介导的细胞死亡和生长因子剥夺似乎激活相同的细胞内途径，涉及JNK信号转导。
Apoptosis may result either from positive induction by ligand binding to a plasma membrane receptor or from negative induction attributable to loss of a suppressor signal. For example, apoptosis of developing sympathetic neurons may be induced in culture either by exposure to leukemia inhibitory factor (LIF) or by deprivation of nerve growth factor. This study compared the cell death pathways activated in sympathetic neurons by these two different stimuli. Both types of cell death were developmentally regulated; both were maximal in the immediate postnatal period and disappeared over the next 2 weeks. Both types of cell death were reduced by genetic deletion of Bax or by virally mediated overexpression of Bcl-2. Similarly both were reduced by inhibition of caspase activity or by inhibition of Nedd-2 synthesis with antisense oligonucleotides. Finally, both involved activation of c-Jun N-terminal kinase (JNK) signaling. Nedd-2 expression by sympathetic neurons declined in parallel with the developmental loss of LIF-mediated cell death, suggesting that downregulation of the caspase during development may underlie the loss of cytokine-mediated apoptosis. Treatment of sympathetic neurons with an antibody that blocks the function of the low-affinity neurotrophin receptor (p75LNTR) prevented LIF-induced cell death. Similarly genetic deletion of p75LNTRprevented apoptosis after LIF treatment. These observations suggest that concurrent p75LNTR signaling is necessary for LIF-induced cell death and that cytokine-mediated cell death and growth factor deprivation appear to activate the same intracellular pathways involving JNK signaling.
白血病抑制因子和神经营养蛋白支持培养物中大鼠结状感觉神经元的重叠群体。
影响因子：
2.7
作者：
Thaler,CD;Suhr,L;Ip,N;Katz,DM
通讯作者：
Katz,DM
体内腺病毒介导的小鼠肝细胞转基因表达的菌株相关变异：免疫活性和免疫缺陷近交菌株之间的比较。
DOI：
--
发表时间：
1995
期刊：
Gene therapy.
影响因子：
--
作者：
Barr,D;Tubb,J;Ferguson,D;Scaria,A;Lieber,A;Wilson,C;Perkins,J;Kay,MA
通讯作者：
Kay,MA
影响因子：
56.9
作者：
GARCIA, I;MARTINOU, I;MARTINOU, JC
通讯作者：
MARTINOU, JC