Biochemical characterization of programmed cell death in NGF-deprived sympathetic neurons.
Biochemical characterization of programmed cell death in NGF-deprived sympathetic neurons.
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NGF 剥夺的交感神经元程序性细胞死亡的生化特征。
DOI：
10.1002/neu.480230911
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
JohnsonJr,EM
中科院分区：
文献类型：
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作者：
Martin,DP;Ito,A;Horigome,K;Lampe,PA;JohnsonJr,EM
当缺乏神经生长因子(NGF)时，年轻的交感神经元就会死亡。在这种情况下，细胞死亡与发育中的神经系统相适应，需要RNA和蛋白质的合成。我们假设在神经元内存在一个内源性死亡程序，该程序被营养因子抑制。构成死亡计划的合成事件所需变化的程度和时间尚不清楚。为了进一步确定导致死亡的生化事件的特征，我们在体外对胚胎大鼠的交感神经元进行了几项实验。当总蛋白合成被≥抑制80%时，用放线菌酮阻断死亡程序。在剥夺NGF后22±4h内抑制蛋白质合成，可防止半数神经元死亡。因此，我们定义蛋白质合成的允许点为22±4小时，类似地，RNA合成的承诺点为26±4小时，NGF救援的承诺点为24±4小时，我们测试了多种化学物质对死亡程序的干扰能力。测试的大多数化合物都无法防止神经元死亡。然而，一些治疗方法确实挽救了缺乏NGF的神经元，并随后进行了表征。其中包括紫外线和提高细胞内cAMP浓度的药物。最后，我们寻找了与其他细胞类型的程序性死亡相关的基因在体外和活体中的神经元表达，包括TRPM-2/SGp-2、多泛素、转化生长因子β-1、c-fos和c-myc。这些基因都没有显示出与神经元死亡相关的显著激活。©1992 John Wiley父子公司
Young sympathetic neurons die when deprived of nerve growth factor (NGF). Under such circumstances, cell death is appropriate to the developing nervous system and requires RNA and protein synthesis. We have hypothesized the existence of an endogenous death program within neurons that is suppressed by trophic factors. The extent and timing of required changes in the synthetic events that comprise the death program are unknown. In an effort to characterize the biochemical events that mediate the death program further, we performed several experiments on embryonic rat sympathetic neuronsin vitro. The death program was blocked with cycloheximide when total protein synthesis was inhibited ≥80%. When protein synthesis was inhibited within 22 ± 4 h of NGF deprivation, death was prevented in half the neurons. Hence, we define thecommitment pointfor protein synthesis to be 22 ± 4 h. Analogously, the commitment point for RNA synthesis was 26 ± 4 h and that for NGF rescue, 24 ± 4 h. We tested the ability of a wide variety of chemicals to interfere with the death program. Most compounds tested were unable to prevent neuronal death. Some treatments, however, did save NGF‐deprived neurons and were subsequently characterized. These included ultraviolet light and agents that raise intracellular concentrations of cAMP. Finally, we looked for the neuronal expressionin vitroandin vivoof genes that have been associated with programmed death in other cell types, including TRPM‐2/SGP‐2, polyubiquitin, TGFβ‐1, c‐fos, and c‐myc. None of these genes showed significant activation associated with neuronal death. © 1992 John Wiley & Sons, Inc.