Opening of plasma membrane voltage-dependent anion channels (VDAC) precedes caspase activation in neuronal apoptosis induced by toxic stimuli
Opening of plasma membrane voltage-dependent anion channels (VDAC) precedes caspase activation in neuronal apoptosis induced by toxic stimuli
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DOI：
10.1038/sj.cdd.4401646
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发表时间：
2005-08-01
影响因子：
12.4
通讯作者：
Ceccatelli, S
中科院分区：
文献类型：
--
作者：
Elinder, F;Akanda, N;Ceccatelli, S
细胞凋亡是中枢神经系统发育和退行性疾病发病的重要过程。K+和Cl-离子的流出导致凋亡细胞的收缩并促进半胱天冬酶的激活。在这里，我们提出的电生理和免疫细胞化学证据激活的电压依赖性阴离子通道（VDAC）在细胞凋亡的神经元的质膜。抗VDAC抗体阻断该通道并抑制凋亡过程。在非凋亡细胞中，质膜VDAC 1蛋白可作为NADH（-铁氰化物）还原酶发挥作用。凋亡细胞中VDAC通道的开放与该活性的增加相关，其部分被VDAC抗体阻断。因此，似乎这种蛋白质在质膜中可能具有双重作用：（1）维持正常细胞中的氧化还原稳态和（2）促进凋亡细胞中的阴离子流出。
Apoptotic cell death is an essential process in the development of the central nervous system and in the pathogenesis of its degenerative diseases. Efflux of K+ and Cl- ions leads to the shrinkage of the apoptotic cell and facilitates the activation of caspases. Here, we present electrophysiological and immunocytochemical evidences for the activation of a voltage-dependent anion channel (VDAC) in the plasma membrane of neurons undergoing apoptosis. Anti-VDAC antibodies blocked the channel and inhibited the apoptotic process. In nonapoptotic cells, plasma membrane VDAC1 protein can function as a NADH(-ferricyanide) reductase. Opening of VDAC channels in apoptotic cells was associated with an increase in this activity, which was partly blocked by VDAC antibodies. Hence, it appears that there might be a dual role for this protein in the plasma membrane: (1) maintenance of redox homeostasis in normal cells and (2) promotion of anion efflux in apoptotic cells.