Fas receptor and neuronal cell death after spinal cord ischemia

Détails

ID Serval
serval:BIB_FFDA57BA7A24
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Fas receptor and neuronal cell death after spinal cord ischemia
Périodique
Journal of Neuroscience
Auteur⸱e⸱s
Matsushita  K., Wu  Y., Qiu  J., Lang-Lazdunski  L., Hirt  L., Waeber  C., Hyman  B. T., Yuan  J., Moskowitz  M. A.
ISSN
0270-6474 (Print)
Statut éditorial
Publié
Date de publication
09/2000
Peer-reviewed
Oui
Volume
20
Numéro
18
Pages
6879-87
Notes
Journal Article Research Support, U.S. Gov't, P.H.S. --- Old month value: Sep 15
Résumé
Cell death from spinal cord injury is mediated in part by apoptotic mechanisms involving downstream caspases (e.g., caspase-3). Upstream mechanisms may involve other caspases such as procaspase-8, a 55 kDa apical caspase, which we found constitutively expressed within spinal cord neurons along with Fas. As early as 1.5 hr after transient ischemia, activated caspase-8 (p18) and caspase-8 mRNA appeared within neurons in intermediate gray matter and in medial ventral horn. We also detected evidence for an increase in death receptor complex by co-immunoprecipitation using Fas and anti-procaspase-8 after ischemia. At early time points, Fas and p18 were co-expressed within individual neurons, as were activated caspase-8 and caspase-3. Moreover, we detected p18 in cells before procaspase-3 cleavage product (p20), suggesting sequential activation. The appearance of cytosolic cytochrome c and gelsolin cleavage after ischemia was consistent with mitochondrial release and caspase-3 activation, respectively. Numerous terminal deoxynucleotidyl transferase-mediated DNA nick end-labeling-positive neurons contained p18 or p20 (65 and 80%, respectively), thereby supporting the idea that cells undergoing cell death contain both processed caspases. Our data are consistent with the idea that transient spinal cord ischemia induces the formation of a death-inducing signaling complex, which may participate in caspase-8 activation and sequential caspase-3 cleavage. Death receptors as well as downstream caspases may be useful therapeutic targets for limiting the death of cells in spinal cord.
Mots-clé
Animals Antigens, CD95/*metabolism *Apoptosis Caspase 3 Caspase 8 Caspase 9 Caspases/genetics/metabolism Cytochrome c Group/metabolism Disease Models, Animal Enzyme Precursors/genetics/metabolism Female Gelsolin/metabolism In Situ Nick-End Labeling Male Mice Mice, Inbred C57BL Neurons/*metabolism/pathology RNA, Messenger/biosynthesis Reperfusion Signal Transduction Spinal Cord/blood supply/*metabolism/pathology Spinal Cord Ischemia/*metabolism/pathology
Pubmed
Web of science
Création de la notice
25/01/2008 12:40
Dernière modification de la notice
20/08/2019 16:30
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