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Apoptotic Volume Decrease (AVD) Is Independent of Mitochondrial Dysfunction and Initiator Caspase Activation
Department of Cell Physiology, National Institute for Physiological Sciences, Okazaki 444-8585, Japan
Laboratory of Immunology, Tokyo Medical and Dental University, Graduate School of Biomedical Science, Tokyo 113-8510, Japan
* Author to whom correspondence should be addressed.
Received: 14 November 2012; in revised form: 24 November 2012 / Accepted: 27 November 2012 / Published: 5 December 2012
(This article belongs to the Special Issue Apoptosis
Abstract: Persistent cell shrinkage is a major hallmark of apoptotic cell death. The early-phase shrinkage, which starts within 30−120 min after apoptotic stimulation and is called apoptotic volume decrease (AVD), is known to be accomplished by activation of K+ channels and volume-sensitive outwardly rectifying (VSOR) Cl− channels in a manner independent of caspase-3 activation. However, it is controversial whether AVD depends on apoptotic dysfunction of mitochondria and activation of initiator caspases. Here, we observed that AVD is induced not only by a mitochondrial apoptosis inducer, staurosporine (STS), in mouse B lymphoma WEHI-231 cells, but also by ligation of the death receptor Fas in human B lymphoblastoid SKW6.4 cells, which undergo Fas-mediated apoptosis without involving mitochondria. Overexpression of Bcl-2 failed to inhibit the STS-induced AVD in WEHI-231 cells. These results indicate that AVD does not require the mitochondrial pathway of apoptosis. In human epithelial HeLa cells stimulated with anti-Fas antibody or STS, the AVD induction was found to precede activation of caspase-8 and caspase-9 and to be resistant to pan-caspase blockers. Thus, it is concluded that the AVD induction is an early event independent of the mitochondrial apoptotic signaling pathway and initiator caspase activation.
Keywords: apoptosis; AVD; mitochondria; caspase-3; caspase-8; caspase-9
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Maeno, E.; Tsubata, T.; Okada, Y. Apoptotic Volume Decrease (AVD) Is Independent of Mitochondrial Dysfunction and Initiator Caspase Activation. Cells 2012, 1, 1156-1167.
Maeno E, Tsubata T, Okada Y. Apoptotic Volume Decrease (AVD) Is Independent of Mitochondrial Dysfunction and Initiator Caspase Activation. Cells. 2012; 1(4):1156-1167.
Maeno, Emi; Tsubata, Takeshi; Okada, Yasunobu. 2012. "Apoptotic Volume Decrease (AVD) Is Independent of Mitochondrial Dysfunction and Initiator Caspase Activation." Cells 1, no. 4: 1156-1167.