Staurosporine-induced neuronal death: multiple mechanisms and methodological implications
Staurosporine-induced neuronal death: multiple mechanisms and methodological implications
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DOI：
10.1038/sj.cdd.4400641
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发表时间：
2000-03-01
影响因子：
12.4
通讯作者：
Johnson, EM
中科院分区：
文献类型：
--
作者：
Deshmukh, M;Johnson, EM
为了研究交感神经元中是否存在多种细胞死亡途径，我们研究了星形孢菌素（STS）诱导的交感神经元中的细胞死亡途径，并将其与具有良好特征的NGF剥夺诱导的死亡途径进行比较。STS浓度的增加，发现诱导不同的生化和形态学特征的交感神经元死亡。100 nM STS诱导的代谢变化，细胞色素c的损失，和半胱天冬酶依赖的形态学变性，这非常类似于由NCF剥夺诱导的凋亡性死亡。相反，用1 μ M STS处理的交感神经元没有显示细胞色素c的损失，但表现出广泛的，半胱天冬酶非依赖性的染色质变化，其为nat TUNEL阳性。1 μ M STS处理的交感神经元代谢活性大大降低，并迅速死亡，但仍保持索马结构，并通过其他标准显示出存活，甚至在STS处理后48小时，说明需要通过多种标准评估细胞死亡。最后，与100 nM STS或1 μ M STS的细胞死亡诱导活性相反，非常低浓度的STS（1 nM STS）通过在NGF剥夺诱导的PCD途径中c-jun磷酸化时或之前起作用来抑制交感神经元死亡。
To examine whether multiple pathways of cell death exist in sympathetic neurons, we studied the cell death pathway induced by staurosporine (STS) in sympathetic neurons and compared it with the well-characterized NGF deprivation-induced death pathway. Increasing concentrations of STS were found to induce sympathetic neuronal death with different biochemical and morphological characteristics. One hundred nM STS induced metabolic changes, loss of cytochrome c, and caspase-dependent morphological degeneration which closely resembled the apoptotic death induced by NCF deprivation, In contrast sympathetic neurons treated with 1 mu M STS showed no loss of cytochrome c but exhibited extensive, caspase-independent, chromatin changes that were nat TUNEL positive. One mu M STS-treated sympathetic neurons had greatly reduced metabolic activities and became committed to die rapidly, yet maintained soma structure and appeared viable by other criteria even up to 48 h after STS treatment, illustrating the need to assess cell death by multiple criteria. Lastly, in contrast to the cell death-inducing activities of 100 nM STS or 1 mu M STS, very low concentrations of STS (1 nM STS) inhibited sympathetic neuronal death by acting either at or prior to c-jun phosphorylation in the NGF deprivation-induced PCD pathway.