Document Detail


Cationic gradient reversal and cytoskeleton-independent volume regulatory pathways define an early stage of apoptosis.
MedLine Citation:
PMID:  18187415     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cell shrinkage, or apoptotic volume decrease (AVD), is a ubiquitous characteristic of programmed cell death that is independent of the death stimulus and occurs in all examples of apoptosis. Here we distinguished two specific stages of AVD based on cell size and a unique early reversal of intracellular ions that occurs in response to activation of both intrinsic and extrinsic cell death signal pathways. The primary stage of AVD is characterized by an early exchange of the normal intracellular ion distribution for sodium from 12 to 113.6 mm and potassium from 139.5 to 30 mm. This early ionic reversal is associated with a 20-40% decrease in cell volume, externalization of phosphatidylserine, loss of mitochondrial membrane potential, and caspase activation and activity along with nuclear condensation that occurs independent of actin cytoskeleton disruption. Disruption of the actin cytoskeleton, however, prevents a secondary stage of AVD in apoptotic cells, characterized by a loss of both potassium and sodium that results in an 80-85% loss in cell volume, DNA degradation, and apoptotic body formation. Together these studies demonstrate that AVD occurs in two distinct stages with the earliest stage reflecting a cellular cationic gradient reversal.
Authors:
Carl D Bortner; Maria I Sifre; John A Cidlowski
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural     Date:  2008-01-10
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  283     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2008 Mar 
Date Detail:
Created Date:  2008-03-10     Completed Date:  2008-05-20     Revised Date:  2013-06-06    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  7219-29     Citation Subset:  IM    
Affiliation:
Laboratory of Signal Transduction, National Institutes of Health Department of Health and Human Services, Research Triangle Park, North Carolina 27709, USA. bortner@niehs.nih.gov
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MeSH Terms
Descriptor/Qualifier:
Apoptosis*
Benzimidazoles / pharmacology
Cations*
Cytoskeleton / metabolism*
DNA / metabolism
Fas Ligand Protein / metabolism
HL-60 Cells
Humans
Ions
Jurkat Cells
Membrane Potentials
Microscopy, Confocal
Mitochondria / metabolism
Models, Biological
Potassium / chemistry
Grant Support
ID/Acronym/Agency:
Z01 ES090079-12/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/Benzimidazoles; 0/Cations; 0/Fas Ligand Protein; 0/Ions; 23491-52-3/HOE 33342; 7440-09-7/Potassium; 9007-49-2/DNA
Comments/Corrections

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