Apoptotic Volume Decrease (AVD) Is Independent of Mitochondrial Dysfunction and Initiator Caspase Activation

Cells

Emi Maeno²  Takeshi Tsubata¹ 

[1] Laboratory of Immunology, Tokyo Medical and Dental University, Graduate School of Biomedical Science, Tokyo 113-8510, Japan; E-Mail:;Department of Cell Physiology, National Institute for Physiological Sciences, Okazaki 444-8585, Japan; E-Mail:

关键词: apoptosis;    AVD;    mitochondria;    caspase-3;    caspase-8;    caspase-9;   

DOI  :  10.3390/cells1041156

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2012 by the authors; licensee MDPI, Basel, Switzerland.