Normotonic cell shrinkage because of disordered volume regulation is an early prerequisite to apoptosis
Normotonic cell shrinkage because of disordered volume regulation is an early prerequisite to apoptosis
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DOI：
10.1073/pnas.140216197
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发表时间：
2000-08-15
影响因子：
11.1
通讯作者：
Okada, Y
中科院分区：
文献类型：
--
作者：
Maeno, E;Ishizaki, Y;Okada, Y
细胞凋亡的一个主要标志是细胞的正常渗透收缩。在这里，我们研究了凋亡细胞萎缩和凋亡细胞死亡的关系。在低渗条件下，三种细胞在两种不同的凋亡诱导剂作用下，AVD的诱导和RVD的易化均先于细胞色素c的释放、caspase-3的激活、DNA阶梯和超微结构的改变，而且广谱的caspase抑制剂不能阻止AVD的发生。当阻断容量调节性Cl-或K+通道来阻止AVD的诱导和RVD的促进时，这些细胞没有表现出后续的凋亡生化和形态事件，并被挽救了死亡。因此，AVD是由细胞体积调节紊乱引起的，是导致细胞死亡的细胞凋亡事件的早期先决条件。
A major hallmark of apoptosis is normotonic shrinkage of cells. Here, we studied the relation between apoptotic cell shrinkage and apoptotic cell death. induction of the apoptotic volume decrease (AVD) under normotonic conditions was found to be coupled to facilitation of the regulatory volume decrease (RVD), which is known to be attained by parallel operation of Cl- and K+ channels, under hypotonic conditions, Both the AVD induction and the RVD facilitation were found to precede cytochrome c release, caspase-3 activation, DNA laddering, and ultrastructural alterations in three cell types after apoptotic insults with two distinct apoptosis inducers, Also, the AVD was not prevented by a broad-spectrum caspase inhibitor. When the AVD induction and the RVD facilitation were prevented by blocking volume-regulatory Cl- or K+ channels, these cells did not show succeeding apoptotic biochemical and morphological events and were rescued from death. Thus, it is concluded that the AVD, which is caused by disordered cell volume regulation, is an early prerequisite to apoptotic events leading to cell death.