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Apoptotic Volume Decrease (AVD) Is Independent of Mitochondrial Dysfunction and Initiator Caspase Activation.
Emi Maeno1, Takeshi Tsubata2, Yasunobu Okada3
1Department of Cell Physiology, National Institute for Physiological Sciences, Okazaki 444-8585, Japan. maenoe@hotmail.com.
Cells
|April 9, 2014
Summary
Early cell shrinkage during apoptosis, known as apoptotic volume decrease (AVD), occurs independently of mitochondrial pathways and caspase activation. This early event involves ion channel activity, not the intrinsic apoptotic signaling cascade.
Area of Science:
- Cell Biology
- Apoptosis Research
- Molecular Mechanisms of Cell Death
Background:
- Cell shrinkage is a key feature of apoptosis.
- Early-phase apoptotic volume decrease (AVD) involves ion channels but its dependence on mitochondria and caspases is debated.
Purpose of the Study:
- To investigate whether AVD requires the mitochondrial apoptosis pathway or initiator caspase activation.
- To clarify the early molecular events preceding caspase activation during apoptosis.
Main Methods:
- Inducing apoptosis via staurosporine (STS) in WEHI-231 cells and Fas ligation in SKW6.4 cells.
- Utilizing Bcl-2 overexpression to assess mitochondrial pathway involvement.
- Stimulating HeLa cells with anti-Fas antibody or STS and monitoring AVD relative to caspase activation.
- Testing resistance to pan-caspase blockers.
Main Results:
- AVD was induced by both mitochondrial (STS) and non-mitochondrial (Fas) pathways.
- Bcl-2 overexpression did not inhibit STS-induced AVD.
- In HeLa cells, AVD preceded caspase-8 and caspase-9 activation and was resistant to pan-caspase blockers.
Conclusions:
- Apoptotic volume decrease (AVD) is an early event in apoptosis.
- AVD is independent of the mitochondrial apoptotic signaling pathway.
- AVD induction does not require initiator caspase activation.
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