Next Article in Journal
Secretome Survey of Human Plexiform Neurofibroma Derived Schwann Cells Reveals a Secreted form of the RARRES1 Protein
Next Article in Special Issue
Implication of Tumor Microenvironment in Chemoresistance: Tumor-Associated Stromal Cells Protect Tumor Cells from Cell Death
Previous Article in Journal
Molecular Characterization and Comparative Sequence Analysis of Defense-Related Gene, Oryza rufipogon Receptor-Like Protein Kinase 1
Previous Article in Special Issue
Decidual Macrophages Are Significantly Increased in Spontaneous Miscarriages and Over-Express FasL: A Potential Role for Macrophages in Trophoblast Apoptosis
Int. J. Mol. Sci. 2012, 13(7), 9363-9379; doi:10.3390/ijms13079363
Article

The Apoptotic Volume Decrease Is an Upstream Event of MAP Kinase Activation during Staurosporine-Induced Apoptosis in HeLa Cells

,
,
 and *
Received: 30 May 2012; in revised form: 18 July 2012 / Accepted: 19 July 2012 / Published: 24 July 2012
(This article belongs to the collection Programmed Cell Death and Apoptosis)
View Full-Text   |   Download PDF [352 KB, updated 19 June 2014; original version uploaded 19 June 2014]   |   Browse Figures
Abstract: Persistent cell shrinkage, called apoptotic volume decrease (AVD), is a pivotal event of apoptosis. Activation of the volume-sensitive outwardly rectifying Cl channel (VSOR) is involved in the AVD induction. On the other hand, activation of the MAP kinase (MAPK) cascade is also known to play a critical role in apoptosis. In the present study, we investigated the relationship between the AVD induction and the stress-responsive MAPK cascade activation during the apoptosis process induced by staurosporine (STS) in HeLa cells. STS was found to induce AVD within 2–5 min and phosphorylation of c-Jun N-terminal kinase (JNK) and p38 MAPK after over 20–30 min. VSOR blockers suppressed not only STS-induced AVD but also phosphorylation of JNK and p38 as well as activation of caspase-3/7. Moreover, a p38 inhibitor, SB203580, and a JNK inhibitor, SP600125, failed to affect STS-induced AVD, whereas these compounds reduced STS-induced activation of caspase-3/7. Also, treatment with ASK1-specific siRNA suppressed STS-induced caspase-3/7 activation without affecting the AVD induction. Furthermore, sustained osmotic cell shrinkage per se was found to trigger phosphorylation of JNK and p38, caspase activation, and cell death. Thus, it is suggested that activation of p38 and JNK is a downstream event of AVD for the STS-induced apoptosis of HeLa cells.
Keywords: apoptosis; MAP kinase; anion channel; shrinkage; volume regulation apoptosis; MAP kinase; anion channel; shrinkage; volume regulation
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Export to BibTeX |
EndNote


MDPI and ACS Style

Hasegawa, Y.; Shimizu, T.; Takahashi, N.; Okada, Y. The Apoptotic Volume Decrease Is an Upstream Event of MAP Kinase Activation during Staurosporine-Induced Apoptosis in HeLa Cells. Int. J. Mol. Sci. 2012, 13, 9363-9379.

AMA Style

Hasegawa Y, Shimizu T, Takahashi N, Okada Y. The Apoptotic Volume Decrease Is an Upstream Event of MAP Kinase Activation during Staurosporine-Induced Apoptosis in HeLa Cells. International Journal of Molecular Sciences. 2012; 13(7):9363-9379.

Chicago/Turabian Style

Hasegawa, Yuichi; Shimizu, Takahiro; Takahashi, Nobuyuki; Okada, Yasunobu. 2012. "The Apoptotic Volume Decrease Is an Upstream Event of MAP Kinase Activation during Staurosporine-Induced Apoptosis in HeLa Cells." Int. J. Mol. Sci. 13, no. 7: 9363-9379.


Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert