Cleavage of plasma membrane calcium pumps by caspases: a link between apoptosis and necrosis.
Cell Death Differ
; 9(8): 818-31, 2002 Aug.
Article
in En
| MEDLINE
| ID: mdl-12107825
ABSTRACT
Neuronal death, which follows ischemic injury or is triggered by excitotoxins, can occur by both apoptosis and necrosis. Caspases, which are not directly required for necrotic cell death, are central mediators of the apoptotic program. Here we demonstrate that caspases cleave and inactivate the plasma membrane Ca(2+) pump (PMCA) in neurons and non-neuronal cells undergoing apoptosis. PMCA cleavage impairs intracellular Ca(2+) handling, which results in Ca(2+) overload. Expression of non-cleavable PMCA mutants prevents the disturbance in Ca(2+) handling, slows down the kinetics of apoptosis, and markedly delays secondary cell lysis (necrosis). These findings suggest that caspase-mediated cleavage and inactivation of PMCAs can lead to necrosis, an event that is reduced by caspase inhibitors in brain ischemia.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cell Membrane
/
Apoptosis
/
Calcium-Transporting ATPases
/
Caspases
/
Hypoxia-Ischemia, Brain
/
Necrosis
/
Neurons
Language:
En
Journal:
Cell Death Differ
Year:
2002
Document type:
Article
Affiliation country:
Germany