title: Reduced NMDA-induced apoptosis in neurons lacking ataxia telangiectasia mutated protein.
abstract: Apoptosis is an important route to neuronal death in experimental models of stroke, the leading neurological cause of death and disability. Here we explore a role for ataxia telangiectasia mutated protein (ATM), an activator of p53, in a primary cortical culture model of stroke. NMDA-induced apoptosis was reduced in cultures derived from mice with targeted deletions in the ATM gene. In addition, NMDA-induced caspase-3 activity was abolished in cultures lacking two functioning copies of the ATM gene. These data provide evidence to suggest that, in primary cortical culture, NMDA-induced apoptosis is partially mediated through ATM. They provide further evidence to support the hypothesis that DNA damage is one route to apoptosis following neuronal injury.
authors.affiliation: Department of Molecular Endocrinology, Molecular Medicine Centre, University of Edinburgh, Crewe Road, Edinburgh, EH4 2XU, UK. malcolm@apoptosis.freeserve.co.uk
authors.forename: Malcolm R
authors.initials: MR
authors.lastname: Macleod
authors.forename: Lynne
authors.initials: L
authors.lastname: Ramage
authors.forename: Ailsa
authors.initials: A
authors.lastname: McGregor
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Seckl
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D004268:DNA-Binding Proteins; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016202:N-Methylaspartate / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency* / Q000235:genetics; D025521:Tumor Suppressor Proteins
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; D016202:N-Methylaspartate; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D017346:Protein Serine-Threonine Kinases