Knock-out of the neural death effector domain protein PEA-15 demonstrates that its expression protects astrocytes from TNFalpha-induced apoptosis.

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.
Mesh Terms:
Amino Acid Sequence, Animals, Apoptosis, Arabidopsis Proteins, Astrocytes, Caspase 8, Caspase 9, Caspases, Cells, Cultured, Corpus Striatum, Embryo, Mammalian, Fatty Acid Desaturases, Mice, Mice, Knockout, Molecular Sequence Data, Neuroglia, Phosphoproteins, Sequence Alignment, Sequence Homology, Amino Acid, Tumor Necrosis Factor-alpha
J. Neurosci.
Date: Oct. 01, 1999
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