title: The plasma membrane Na+/Ca2+ exchanger is cleaved by distinct protease families in neuronal cell death.
abstract: 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 Ca2+ 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 Ca2+ deregulation leading to necrosis is due to calpain-mediated modulation of the plasma membrane Na+/Ca2+ 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 Ca2+ extrusion pathway is a lethal event in multiple forms of cell death.
authors: MRC Toxicology Unit, University of Leicester, Hodgkin Building, Lancaster Road LE1 9HN, Leicester, UK. db81@le.ac.uk
authors: D
authors: D
authors: Bano
authors: E
authors: E
authors: Munarriz
authors: H L
authors: HL
authors: Chen
authors: E
authors: E
authors: Ziviani
authors: G
authors: G
authors: Lippi
authors: K W
authors: KW
authors: Young
authors: P
authors: P
authors: Nicotera
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D016895:Culture Media, Serum-Free; D006801:Humans; D006868:Hydrolysis; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger / Q000378:metabolism*
chemical_list: D016895:Culture Media, Serum-Free; D019831:Sodium-Calcium Exchanger; D010447:Peptide Hydrolases