Activation of G Proteins Bidirectionally Affects Apoptosis of Cultured Cerebellar Granule Neurons

Activation of G Proteins Bidirectionally Affects Apoptosis of Cultured Cerebellar Granule Neurons
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G蛋白的激活双向影响培养的小脑颗粒神经元的凋亡

DOI:
10.1046/j.1471-4159.1995.65062425.x
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发表时间:
1995
影响因子:
4.7
通讯作者:
S. Paul
S. Paul
中科院分区:
医学2区
文献类型:
--
作者:
G. Yan;Suizhen Lin;R. P. Irwin;S. Paul

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摘要:培养的小脑颗粒神经元维持在去极化浓度的K+(25 MM),然后切换到生理浓度的K+(5 MM),发生凋亡。我们现在报道,特定G蛋白的激活强烈地和双向地影响培养的大鼠小脑颗粒神经元的凋亡。用霍乱毒素刺激Gs可完全阻断非去极化浓度K+所诱导的细胞凋亡,而用黄蜂毒多肽Mastoparan刺激GO/GI即使在高浓度K+时也能诱导小脑颗粒神经元的凋亡。此外,霍乱毒素对小脑颗粒神经元的预处理可减轻马斯托卡兰诱导的神经元死亡。相比之下,百日咳毒素、环磷酸腺苷的细胞通透性类似物和蛋白激酶A的激活剂不影响培养的小脑颗粒神经元的凋亡。这些数据表明,G蛋白可能是控制哺乳动物神经元程序性死亡的关键开关,特别是在发育中的中枢神经系统。
Abstract: Cultured cerebellar granule neurons maintained in depolarizing concentrations of K+ (25 mM) and then switched to physiological concentrations of K+ (5 mM) undergo apoptosis. We now report that activation of specific G proteins robustly and bidirectionally affects apoptosis of cultured rat cerebellar granule neurons. Stimulation of Gs with cholera toxin completely blocks apoptosis induced by nondepolarizing concentrations of K+, whereas stimulation of Go/Gi with the wasp venom peptide mastoparan induces apoptosis of cerebellar granule neurons even in high (depolarizing) concentrations of K+. Moreover, pretreatment of cerebellar granule neurons with cholera toxin attenuates neuronal death induced by mastoparan. By contrast, pertussis toxin, cell‐permeable analogues of cyclic AMP, and activators of protein kinase A do not affect apoptosis of cultured cerebellar granule neurons. These data suggest that G proteins may function as key switches for controlling the programmed death of mammalian neurons, especially in the developing CNS.
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