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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B*
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
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ATP-Binding Cassette Transporters / metabolism*
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Animals
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Annexin A5 / metabolism
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Apoptosis / physiology*
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Biomarkers
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Carrier Proteins / metabolism*
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Cell Cycle
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Fas Ligand Protein
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Humans
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Leukemia-Lymphoma, Adult T-Cell / pathology
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Membrane Glycoproteins / physiology
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Membrane Lipids / metabolism*
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Membrane Proteins / metabolism*
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Mice
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Models, Biological
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Neutrophils / metabolism
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Phagocytosis
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Phosphatidylserines / metabolism*
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Phospholipid Transfer Proteins*
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Proto-Oncogene Proteins / physiology*
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Proto-Oncogene Proteins c-abl / physiology*
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Proto-Oncogene Proteins c-bcl-2
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Recombinant Fusion Proteins / biosynthesis
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Thymus Gland / cytology
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Transfection
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Tumor Cells, Cultured
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fas Receptor / physiology
Substances
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ATP Binding Cassette Transporter, Subfamily B
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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ATP-Binding Cassette Transporters
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Annexin A5
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Biomarkers
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Carrier Proteins
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FASLG protein, human
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Fas Ligand Protein
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Fasl protein, mouse
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Membrane Glycoproteins
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Membrane Lipids
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Membrane Proteins
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Phosphatidylserines
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Phospholipid Transfer Proteins
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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Recombinant Fusion Proteins
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fas Receptor
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multidrug resistance protein 3
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Proto-Oncogene Proteins c-abl