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Title: Upstream control of apoptosis by caspase-2 in serum-deprived primary neurons. Author: Chauvier D, Lecoeur H, Langonné A, Borgne-Sanchez A, Mariani J, Martinou JC, Rebouillat D, Jacotot E. Journal: Apoptosis; 2005 Dec; 10(6):1243-59. PubMed ID: 16215683. Abstract: During development as well as in pathological situations, neurons that fail to find appropriate targets or neurotrophic factors undergo cell death. Using primary cortical neurons subjected to acute serum-deprivation (SD), we have examined caspases activation, mitochondrial dysfunction and cell death parameters. Among a panel of metabolic, signaling and caspases inhibitors only those able to interfere with caspase-2 like activity protect primary neurons against SD-induced cell death. In situ detection and subcellular fractionation demonstrate a very early activation of cytosolic caspase-2, which controls Bax cleavage, relocalization and mitochondrial membrane permeabilization (MMP). Both z-VDVAD-fmk and a siRNA specific for caspase-2 abolish Bax changes, mitochondrial membranes permeabilization, as well as cytochrome c release-dependent activation of caspase-9/caspase-3, nuclear alterations, phosphatidylserine exposure, neurites dismantling and neuronal death. Hence, caspase-2 is an early checkpoint for apoptosis initiation in primary neurons subjected to serum deprivation.[Abstract] [Full Text] [Related] [New Search]