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.
Kitsberg
D
D
Harvard Medical School, Boston, Massachusetts 02115, USA.
Formstecher
E
E
Fauquet
M
M
Kubes
M
M
Cordier
J
J
Canton
B
B
Pan
G
G
Rolli
M
M
Glowinski
J
J
Chneiweiss
H
H
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D029681:Arabidopsis Proteins; D001253:Astrocytes / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000737:chemistry / Q000378:metabolism; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000166:cytology* / Q000502:physiology; D004622:Embryo, Mammalian; D044943:Fatty Acid Desaturases / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009457:Neuroglia / Q000166:cytology / Q000502:physiology; D010750:Phosphoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D051017:Apoptosis Regulatory Proteins; D029681:Arabidopsis Proteins; C490444:Pea15 protein, mouse; D010750:Phosphoproteins; D014409:Tumor Necrosis Factor-alpha; D044943:Fatty Acid Desaturases; C084083:Fad7 protein, Arabidopsis; C505526:Casp8 protein, mouse; C506434:Casp9 protein, mouse; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases