title: Differential regulation of the intrinsic pathway of apoptosis in brain and liver during ageing.
abstract: The intrinsic (mitochondria-dependent) pathway of apoptosis is one of the major pathways leading to cell death. We evaluated cytochrome c/apoptotic protease activation factor-1 (Apaf-1)-dependent activation of caspase-3 in brain and liver of different strains of rodents at different stages of development. In cell-free extracts from brain and liver of Sprague-Dawley rats, caspase was activated by cytochrome c/2'-deoxyadenosine 5'-triphosphate at both neonatal and adult stages. In adult brain extracts from Wistar rats, no activation of caspase was observed while extracts from neonatal brain and liver and from adult liver were activated. In CD-1 mouse, only neonatal extracts were activated. Alteration in levels of endogenous inhibitors of apoptosis were not responsible for the lack of activation observed. Instead, decrease in the content of Apaf-1 and caspase-3 and some degradation of caspase-9 during brain ageing were observed. These results suggest that a decrease in apoptosis activation during ageing is not tissue-specific, but rather displays a complex dependence on species and strains of animals.
authors.affiliation: Buck Institute for Age Research, 8001 Redwood Blvd., Novato, CA 94945, USA.
authors.forename: Veronika
authors.initials: V
authors.lastname: Stoka
authors.forename: Vito
authors.initials: V
authors.lastname: Turk
authors.forename: Dale E
authors.initials: DE
authors.lastname: Bredesen
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D017209:Apoptosis; D053477:Apoptotic Protease-Activating Factor 1; D001921:Brain / Q000166:cytology* / Q000378:metabolism; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D045304:Cytochromes c / Q000378:metabolism; D003838:Deoxyadenine Nucleotides / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008099:Liver / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D011506:Proteins / Q000378:metabolism; D051381:Rats; D013045:Species Specificity
chemical_list: C506592:APAF1 protein, human; C506593:Apaf1 protein, mouse; C506594:Apaf1 protein, rat; D053477:Apoptotic Protease-Activating Factor 1; D003838:Deoxyadenine Nucleotides; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D045304:Cytochromes c; C506433:CASP9 protein, human; C506434:Casp9 protein, mouse; C506435:Casp9 protein, rat; D053453:Caspase 9; D020169:Caspases; C026600:2'-deoxyadenosine triphosphate