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The Plasma Membrane Na + /Ca 2+ Exchanger Is Cleaved by Distinct Protease Families in Neuronal Cell Death
Author(s) -
BANO D.,
MUNARRIZ E.,
CHEN H. L.,
ZIVIANI E.,
LIPPI G.,
YOUNG K. W.,
NICOTERA P.
Publication year - 2007
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1387.006
Subject(s) - protease , microbiology and biotechnology , membrane , chemistry , programmed cell death , biophysics , biology , biochemistry , enzyme , apoptosis
Neurodegenerative conditions commonly involve loss of neuronal connectivity, synaptic dysfunction with excessive pruning, and ionic imbalances. These often serve as a prelude to cell death either through the activation of apoptotic or necrotic death routines or excess autophagy. In many instances, a local or generalized Ca 2+ deregulation is involved in signaling or executing cell death. We have recently shown that in brain ischemia, and during excitotoxicity triggered by excess glutamate, the irreversible Ca 2+ deregulation leading to necrosis is due to calpain‐mediated modulation of the plasma membrane Na + /Ca 2+ exchanger (NCX). Here we show that the NCX can also be cleaved by caspases in neurons undergoing apoptosis, which suggests that cleavage of the main Ca 2+ extrusion pathway is a lethal event in multiple forms of cell death.