Involvement of the proteasome in the programmed cell death of NGF-deprived sympathetic neurons
Détails
ID Serval
serval:BIB_84D793ACD8EC
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Involvement of the proteasome in the programmed cell death of NGF-deprived sympathetic neurons
Périodique
EMBO Journal
ISSN
0261-4189 (Print)
Statut éditorial
Publié
Date de publication
08/1996
Volume
15
Numéro
15
Pages
3845-52
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Aug 1
Research Support, Non-U.S. Gov't --- Old month value: Aug 1
Résumé
Sympathetic neurons undergo programmed cell death (PCD) upon deprivation of nerve growth factor (NGF). PCD of neurons is blocked by inhibitors of the interleukin-1beta converting enzyme (ICE)/Ced-3-like cysteine protease, indicating involvement of this class of proteases in the cell death programme. Here we demonstrate that the proteolytic activities of the proteasome are also essential in PCD of neurons. Nanomolar concentrations of several proteasome inhibitors, including the highly selective inhibitor lactacystin, not only prolonged survival of NGF-deprived neurons but also prevented processing of poly(ADP-ribose) polymerase which is known to be cleaved by an ICE/Ced-3 family member during PCD. These results demonstrate that the proteasome is a key regulator of neuronal PCD and that, within this process, it is involved upstream of proteases of the ICE/Ced-3 family. This order of events was confirmed in macrophages where lactacystin inhibited the proteolytic activation of precursor ICE and the subsequent generation of active interleukin-1beta.
Mots-clé
Acetylcysteine/analogs & derivatives/pharmacology
Animals
*Apoptosis
Calcium-Binding Proteins/metabolism
Caspase 1
Cell Survival/drug effects
Cysteine Endopeptidases/metabolism/*physiology
Cysteine Proteinase Inhibitors/pharmacology
DNA Ligases/metabolism
Electrophoresis, Polyacrylamide Gel
Leupeptins/pharmacology
Multienzyme Complexes/*physiology
Nerve Growth Factors/*physiology
Neurons/*cytology
Poly(ADP-ribose) Polymerases/metabolism
Proteasome Endopeptidase Complex
Rats
Sympathetic Nervous System/*cytology
Pubmed
Web of science
Création de la notice
24/01/2008 16:19
Dernière modification de la notice
20/08/2019 15:44