QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 15 January 2008
doi: 10.1242/jcs.017343

This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: jcs.017343v1 121/3/290    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ernest, N. J. Articles by Sontheimer, H. Search for Related Content PubMed PubMed Citation Articles by Ernest, N. J. Articles by Sontheimer, H. Social Bookmarking                         What's this?

Cytoplasmic condensation is both necessary and sufficient to induce apoptotic cell death

Department of Neurobiology, the Civitan International Research Center, and the Center for Glial Biology in Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA

^* Author for correspondence (e-mail: hws{at}uab.edu)

Accepted 5 November 2007

Programmed cell death (apoptosis) is important in tissue maintenance. Hallmarks of apoptosis include caspase activation, DNA fragmentation and an overall reduction in cell volume. Whether this apoptotic volume decrease (AVD) is a mere response to initiators of apoptosis or whether it is functionally significant is not clear. In this study, we sought to answer this question using human malignant glioma cells as a model system. In vivo, high grade gliomas demonstrate an increased percentage of apoptotic cells as well as upregulation of death ligand receptors. By dynamically monitoring cell volume, we show that the induction of apoptosis, via activation of either the intrinsic or extrinsic pathways with staurosporine or TRAIL, respectively, resulted in a rapid AVD in D54-MG human glioma cells. This decrease in cell volume could be prevented by inhibiting the efflux of Cl^– through channels. Such suppression of AVD also reduced the activation of caspases 3, 8 and 9 and suppressed DNA fragmentation. Importantly, experimental manipulations that reduce the cell volume to 70% of the original volume for periods of at least 3 hours were sufficient to initiate apoptosis even in the absence of death ligands. Hence, this data suggests that cell condensation is both necessary and sufficient for the induction of apoptosis.

Key words: KCC, Apoptosis, Apoptotic volume decrease (AVD), Cell condensation, Chloride channels, Glioma

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

Related articles in JCS:

Death by shrinkage

JCS 2008 121: 302. [Full Text]  

This article has been cited by other articles:

				E. H. Zhou, X. Trepat, C. Y. Park, G. Lenormand, M. N. Oliver, S. M. Mijailovich, C. Hardin, D. A. Weitz, J. P. Butler, and J. J. Fredberg Universal behavior of the osmotically compressed cell and its analogy to the colloidal glass transition PNAS, June 30, 2009; 106(26): 10632 - 10637. [Abstract] [Full Text] [PDF]

				R. Franco, W. I. DeHaven, M. I. Sifre, C. D. Bortner, and J. A. Cidlowski Glutathione Depletion and Disruption of Intracellular Ionic Homeostasis Regulate Lymphoid Cell Apoptosis J. Biol. Chem., December 26, 2008; 283(52): 36071 - 36087. [Abstract] [Full Text] [PDF]