Early redistribution of plasma membrane phosphatidylserine is a general feature of apoptosis regardless of the initiating stimulus: inhibition by overexpression of Bcl-2 and Abl.
Seamus J. Martin,Chris P. M. Reutelingsperger,A J McGahon,J. A. Rader,R. C. A. A. Van Schie,Drake LaFace,Douglas R. Green +6 more
TLDR
It is shown that PS externalization is an early and widespread event during apoptosis of a variety of murine and human cell types, regardless of the initiating stimulus, and precedes several other events normally associated with this mode of cell death.Abstract:
A critical event during programmed cell death (PCD) appears to be the acquisition of plasma membrane (PM) changes that allows phagocytes to recognize and engulf these cells before they rupture. The majority of PCD seen in higher organisms exhibits strikingly similar morphological features, and this form of PCD has been termed apoptosis. The nature of the PM changes that occur on apoptotic cells remains poorly defined. In this study, we have used a phosphatidylserine (PS)-binding protein (annexin V) as a specific probe to detect redistribution of this phospholipid, which is normally confined to the inner PM leaflet, during apoptosis. Here we show that PS externalization is an early and widespread event during apoptosis of a variety of murine and human cell types, regardless of the initiating stimulus, and precedes several other events normally associated with this mode of cell death. We also report that, under conditions in which the morphological features of apoptosis were prevented (macromolecular synthesis inhibition, overexpression of Bcl-2 or Abl), the appearance of PS on the external leaflet of the PM was similarly prevented. These data are compatible with the notion that activation of an inside-outside PS translocase is an early and widespread event during apoptosis.read more
Citations
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The Release of Cytochrome c from Mitochondria: A Primary Site for Bcl-2 Regulation of Apoptosis
TL;DR: In a cell-free apoptosis system, mitochondria spontaneously released cytochrome c, which activated DEVD-specific caspases, leading to fodrin cleavage and apoptotic nuclear morphology, and Bcl-2 acts to inhibit cy tochrome c translocation, thereby blocking caspase activation and the apoptotic process.
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The Nuclear Factor NF-κB Pathway in Inflammation
TL;DR: How genetic evidence in mice has revealed complex roles for the NF-kappaB in inflammation that suggest both pro- and anti-inflammatory roles for this pathway is described.
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Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF.
TL;DR: The results suggest that binding and/or phagocytosis of apoptotic cells induces active antiinflammatory or suppressive properties in human macrophages, likely that resolution of inflammation depends not only on the removal of apoptosis but on active suppression of inflammatory mediator production.
Mammalian caspases: structure ,a ctivation ,s ubstrates, and functions during apoptosis
TL;DR: Caspases, a family of cysteine-dependent aspartate-directed proteases, are prominent among the death proteases as discussed by the authors, and they play critical roles in initiation and execution of this process.
Journal ArticleDOI
Mammalian Caspases: Structure, Activation, Substrates, and Functions During Apoptosis
TL;DR: This work has shown that apoptotic cell death is a genetically programmed, morphologically distinct form of cell death that can be triggered by a variety of physiological and pathological stimuli, and that proteases play critical roles in initiation and execution of this process.
References
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Journal ArticleDOI
Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics.
TL;DR: Apoptosis seems to be involved in cell turnover in many healthy adult tissues and is responsible for focal elimination of cells during normal embryonic development, and participates in at least some types of therapeutically induced tumour regression.
Book ChapterDOI
Cell death : the significance of apoptosis
TL;DR: It has proved feasible to categorize most if not all dying cells into one or the other of two discrete and distinctive patterns of morphological change, which have, generally, been found to occur under disparate but individually characteristic circumstances.
Journal Article
Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages.
Valerie A. Fadok,Dennis R. Voelker,Priscilla A. Campbell,J. John Cohen,D L Bratton,Peter M. Henson +5 more
TL;DR: The data suggest that macrophages specifically recognize phosphatidylserine that is exposed on the surface of lymphocytes during the development of apoptosis, and suggest that apoptotic lymphocytes lose membrane phospholipid asymmetry and expose phosphorus on the outer leaflet of the plasma membrane.
Journal ArticleDOI
Social controls on cell survival and cell death
TL;DR: For some mammalian cells, programmed death seems to occur by default unless suppressed by signals from other cells, so dependence on specific survival signals provides a simple way to eliminate misplaced cells, for regulating cell numbers and, perhaps, for selecting the fittest cells.
Journal ArticleDOI
Annexin V for flow cytometric detection of phosphatidylserine expression on B cells undergoing apoptosis.
Gerrit Koopman,Chris P. M. Reutelingsperger,G. A. M. Kuijten,R. M. J. Keehnen,Steven T. Pals,M. H. J. Van Oers +5 more
TL;DR: The results indicate that the phase in apoptosis that is characterized by chromatin condensation coincides with phosphatidylserine exposure, which precedes membrane damage that might lead to release from the cells of enzymes that are harmful to the surrounding tissues.