Bioenergetic analysis of cerebellar granule neurons undergoing apoptosis by potassium/serum deprivation
Bioenergetic analysis of cerebellar granule neurons undergoing apoptosis by potassium/serum deprivation
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DOI：
10.1038/sj.cdd.4401851
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发表时间：
2006-09-01
影响因子：
12.4
通讯作者：
Nicholls, D. G.
中科院分区：
文献类型：
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作者：
Jekabsons, M. B.;Nicholls, D. G.
K+/血清剥夺（低K+）诱导的小脑颗粒神经元凋亡已被广泛研究。线粒体通过向细胞质中释放促凋亡因子在细胞凋亡中起关键作用，并且线粒体功能障碍已被提出为该模型中的早期或起始事件。为了直接检验这一假设，细胞和线粒体的生物能量通过确定盖玻片连接的神经元的呼吸参数进行定量。低K+时氧化磷酸化率下降39-49%，这是由于细胞ATP需求减少，而不是ATP/ADP交换受损或呼吸链抑制。从3到5小时，在低K+，细胞凋亡的进展从13至40%，尽管没有明显的变化，呼吸参数。用二氢乙锭评估的稳态O-2（-）的变化见于颗粒神经元，而非海马神经元。O-2（-）的变化与[Ca 2 +]（c）的变化相关，但与线粒体呼吸无关。因此，在这种常见的神经元凋亡模型中，可以排除早期线粒体功能障碍。
Apoptosis induced by K+/serum deprivation (low K+) in cerebellar granule neurons has been extensively investigated. The mitochondria play a key role in apoptosis by releasing proapoptotic factors into the cytoplasm, and mitochondrial dysfunction has been proposed as an early or initiating event in this model. To directly test this hypothesis, cellular and mitochondrial bioenergetics were quantified by determining the respiratory parameters of coverslip-attached neurons. While oxidative phosphorylation rate decreased 39-49% in low K+, this was due to decreased cellular ATP demand rather than impaired ATP/ADP exchange or respiratory chain inhibition. From 3 to 5 h in low K+, apoptosis progressed from 13 to 40% despite no appreciable change in respiratory parameters. Changes in steady-state O-2(-), assessed with dihydroethidium, were seen in granule but not hippocampal neurons. The O-2(-) change correlated with changes in [Ca2+](c), but not mitochondrial respiration. Thus, early mitochondrial dysfunction can be excluded in this common model of neuronal apoptosis.