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Published on: January 26, 2019
The apoptotic volume decrease is an upstream event of MAP kinase activation during Staurosporine-induced apoptosis in
Yuichi Hasegawa1, Takahiro Shimizu1, Nobuyuki Takahashi1
1Department of Cell Physiology, National Institute for Physiological Sciences, Okazaki 444-8585, Japan.
International Journal of Molecular Sciences
|September 4, 2012
Summary
Apoptotic volume decrease (AVD) precedes MAP kinase (MAPK) activation in staurosporine-induced apoptosis. Cell shrinkage triggers JNK and p38 MAPK pathways, indicating AVD is upstream of MAPK signaling in HeLa cells.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Apoptosis involves cell shrinkage (apoptotic volume decrease, AVD) and MAP kinase (MAPK) cascade activation.
- The volume-sensitive outwardly rectifying Cl(-) channel (VSOR) is implicated in AVD induction.
Purpose of the Study:
- To investigate the relationship between AVD and stress-responsive MAPK cascade activation during staurosporine (STS)-induced apoptosis in HeLa cells.
Main Methods:
- Induction of apoptosis using staurosporine (STS) in HeLa cells.
- Treatment with VSOR blockers, p38 inhibitor (SB203580), JNK inhibitor (SP600125), and ASK1-specific siRNA.
- Assessment of AVD, MAPK phosphorylation (JNK, p38), and caspase-3/7 activation.
Main Results:
- STS induced AVD rapidly (2-5 min), preceding JNK and p38 phosphorylation (20-30 min).
- VSOR blockers inhibited STS-induced AVD, JNK/p38 phosphorylation, and caspase activation.
- p38 and JNK inhibitors did not affect STS-induced AVD but reduced caspase activation.
- ASK1-siRNA suppressed caspase activation without affecting AVD.
- Sustained osmotic cell shrinkage induced JNK/p38 phosphorylation, caspase activation, and cell death.
Conclusions:
- MAPK (p38 and JNK) activation is a downstream event of AVD in STS-induced apoptosis of HeLa cells.
- AVD appears to be an upstream signaling event initiating the MAPK cascade during apoptosis.
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