Cleavage of plasma membrane calcium pumps by caspases : a link between apoptosis and necrosis

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2002
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Schwab, Birgit Lisa
Guerini, Danilo
Didszun, C.
Bano, Daniele
Fava, Eugenio
Tam, John
Xu, D.
Xanthoudakis, Steve
Nicholson, Donald W.
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Cell Death and Differentiation. 2002, 9(8), pp. 818-831. ISSN 1350-9047. Available under: doi: 10.1038/sj.cdd.4401042
Zusammenfassung

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 centralmediators of the apoptotic program.Herewe demonstrate that caspases cleave and inactivate the plasma membrane Ca2+ pump (PMCA) in neurons and non-neuronal cells undergoing apoptosis. PMCA cleavage impairs intracellular Ca2+ handling, which results in Ca2+ overload. Expression of non-cleavable PMCA mutants prevents the disturbance in Ca2+ 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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570 Biowissenschaften, Biologie
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ISO 690SCHWAB, Birgit Lisa, Danilo GUERINI, C. DIDSZUN, Daniele BANO, Elisa FERRANDO-MAY, Eugenio FAVA, John TAM, D. XU, Steve XANTHOUDAKIS, Donald W. NICHOLSON, Ernesto CARAFOLI, Pierluigi NICOTERA, 2002. Cleavage of plasma membrane calcium pumps by caspases : a link between apoptosis and necrosis. In: Cell Death and Differentiation. 2002, 9(8), pp. 818-831. ISSN 1350-9047. Available under: doi: 10.1038/sj.cdd.4401042
BibTex
@article{Schwab2002-08Cleav-18247,
  year={2002},
  doi={10.1038/sj.cdd.4401042},
  title={Cleavage of plasma membrane calcium pumps by caspases : a link between apoptosis and necrosis},
  number={8},
  volume={9},
  issn={1350-9047},
  journal={Cell Death and Differentiation},
  pages={818--831},
  author={Schwab, Birgit Lisa and Guerini, Danilo and Didszun, C. and Bano, Daniele and Ferrando-May, Elisa and Fava, Eugenio and Tam, John and Xu, D. and Xanthoudakis, Steve and Nicholson, Donald W. and Carafoli, Ernesto and Nicotera, Pierluigi}
}
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