Cationic gradient reversal and cytoskeleton-independent volume regulatory pathways define an early stage of apoptosis
Cationic gradient reversal and cytoskeleton-independent volume regulatory pathways define an early stage of apoptosis
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DOI：
10.1074/jbc.m707809200
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发表时间：
2008-03-14
影响因子：
4.8
通讯作者：
Cidlowski, John A.
中科院分区：
文献类型：
--
作者：
Bortner, Carl D.;Sifre, Maria I.;Cidlowski, John A.
细胞收缩或凋亡体积减少（AVD）是程序性细胞死亡的普遍特征，其独立于死亡刺激并且发生在所有凋亡的实例中。在这里，我们区分了两个特定阶段的AVD的细胞大小和一个独特的早期逆转的细胞内离子，发生在激活内源性和外源性细胞死亡信号通路。AVD的初级阶段的特征在于正常细胞内离子分布的早期交换，钠从12 mM变为113.6 mM，钾从139.5 mM变为30 mM。这种早期离子逆转与细胞体积减少20 - 40%、磷脂酰丝氨酸外化、线粒体膜电位丧失、以及半胱天冬酶活化和活性沿着与肌动蛋白细胞骨架破坏无关的核浓缩。然而，肌动蛋白细胞骨架的破坏阻止了凋亡细胞中AVD的第二阶段，其特征在于钾和钠的损失，导致细胞体积损失80 - 85%，DNA降解和凋亡小体形成。总之，这些研究表明，AVD发生在两个不同的阶段，最早的阶段反映了细胞阳离子梯度逆转。
Cell shrinkage, or apoptotic volume decrease ( AVD), is a ubiquitous characteristic of programmed cell death that is independent of the death stimulus and occurs in all examples of apoptosis. Here we distinguished two specific stages of AVD based on cell size and a unique early reversal of intracellular ions that occurs in response to activation of both intrinsic and extrinsic cell death signal pathways. The primary stage of AVD is characterized by an early exchange of the normal intracellular ion distribution for sodium from 12 to 113.6 mM and potassium from 139.5 to 30 mM. This early ionic reversal is associated with a 20 - 40% decrease in cell volume, externalization of phosphatidylserine, loss of mitochondrial membrane potential, and caspase activation and activity along with nuclear condensation that occurs independent of actin cytoskeleton disruption. Disruption of the actin cytoskeleton, however, prevents a secondary stage of AVD in apoptotic cells, characterized by a loss of both potassium and sodium that results in an 80 - 85% loss in cell volume, DNA degradation, and apoptotic body formation. Together these studies demonstrate that AVD occurs in two distinct stages with the earliest stage reflecting a cellular cationic gradient reversal.