Abstract
Apoptosis is a very general phenomenon, but only a few reports concern astrocytes. Indeed, astrocytes express receptors for tumor necrosis factor (TNF) alpha, a cytokine demonstrated on many cells and tissues to mediate apoptosis after recruitment of adaptor proteins containing a death effector domain (DED). PEA-15 is a DED-containing protein prominently expressed in the CNS and particularly abundant in astrocytes. This led us to investigate if PEA-15 expression could be involved in astrocytic protection against deleterious effects of TNF. In vitro assays evidence that PEA-15 may bind to DED-containing protein FADD and caspase-8 known to be apical adaptors of the TNF apoptotic signaling. After generation of PEA-15 null mutant mice, our results demonstrate that PEA-15 expression increases astrocyte survival after exposure to TNF.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Apoptosis / drug effects
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Apoptosis / physiology*
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Apoptosis Regulatory Proteins
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Arabidopsis Proteins*
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Astrocytes / cytology*
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Astrocytes / drug effects
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Astrocytes / physiology*
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Caspase 8
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Caspase 9
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Caspases / chemistry
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Caspases / metabolism
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Cells, Cultured
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Corpus Striatum / cytology*
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Corpus Striatum / physiology
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Embryo, Mammalian
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Fatty Acid Desaturases / chemistry
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Fatty Acid Desaturases / metabolism
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Mice
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Mice, Knockout
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Molecular Sequence Data
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Neuroglia / cytology
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Neuroglia / physiology
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Phosphoproteins / deficiency
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Phosphoproteins / genetics
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Phosphoproteins / metabolism*
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Sequence Alignment
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Sequence Homology, Amino Acid
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Tumor Necrosis Factor-alpha / pharmacology*
Substances
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Apoptosis Regulatory Proteins
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Arabidopsis Proteins
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Pea15 protein, mouse
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Phosphoproteins
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Tumor Necrosis Factor-alpha
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Fatty Acid Desaturases
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Fad7 protein, Arabidopsis
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Casp8 protein, mouse
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Casp9 protein, mouse
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Caspase 8
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Caspase 9
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Caspases