Cleavage of plasma membrane calcium pumps by caspases: a link between apoptosis and necrosis
| Autor: | Elisa Ferrando-May, Eugenio Fava, Steve Xanthoudakis, Pierluigi Nicotera, Daigen Xu, D Guerini, Donald W. Nicholson, C Didszun, John Tam, Ernesto Carafoli, B L Schwab, D Bano |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Intracellular Fluid
Lysis Necrosis Calcium pump Neurotoxins Apoptosis CHO Cells Calcium-Transporting ATPases Cleavage (embryo) Brain ischemia Mice Plasma Membrane Calcium-Transporting ATPases ddc:570 Cricetinae medicine Animals Calcium Signaling Coloring Agents Molecular Biology Cation Transport Proteins Caspase Neurons Binding Sites biology Caspase 3 Cell Membrane Cell Biology medicine.disease Immunohistochemistry Cell biology Clone Cells Rats Animals Newborn Caspases Hypoxia-Ischemia Brain Mutation biology.protein Calcium medicine.symptom Intracellular |
| Zdroj: | Cell death and differentiation. 9(8) |
| ISSN: | 1350-9047 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|