title: Expression pattern of ataxia telangiectasia mutated (ATM), p53, Akt, and glycogen synthase kinase-3β in the striatum of rats treated with 3-nitropropionic acid.
abstract: 3-Nitropropionic acid (3-NPA) is a mitochondrial toxin used in the laboratory to replicate neurodegenerative conditions that are accompanied by degeneration of the caudate-putamen. 3-NPA induces depletion in ATP production, reactive oxygen species production, and secondary excitotoxicity mediated by activation of N-methyl-D-aspartate receptors that culminates in the triggering of cell death mechanisms, including apoptosis. We here examined by immunohistochemical methods whether cellular expression of phospho(Ser1981) -ataxia telangiectasia mutated (ATM), phospho(Ser15) -p53, phospho(Ser473) -Akt, and phospho(Ser9) -glycogen synthase kinase-3β (GSK3β), which are key signal molecules that play a critical role in regulating cellular processes related to cell survival and demise, were involved in the striatal neurodegeneration in the brains of rats treated with 3-NPA. Our results indicate that the toxin induced the activation of ATM and p53 only in astrocytes, and a role for these proteins in neuronal degeneration was ruled out. On the other hand, striatal neurons lost the active form of Akt as soon as they began to appear pyknotic, indicating impairment of the PI3K/Akt/GSK3 pathway in their degenerative process. The inactive form of GSK3β was detected extensively, mainly in the rim of the striatal lesions around degenerating neurons, which could be attributed to a cell death or cell survival response.
authors.affiliation: Departament de Fisiologia, Facultat de Farmàcia, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Joaquim
authors.initials: J
authors.lastname: Duran-Vilaregut
authors.forename: Gemma
authors.initials: G
authors.lastname: Manich
authors.forename: Jaume
authors.initials: J
authors.lastname: Del Valle
authors.forename: Antoni
authors.initials: A
authors.lastname: Camins
authors.forename: Mercè
authors.initials: M
authors.lastname: Pallàs
authors.forename: Jordi
authors.initials: J
authors.lastname: Vilaplana
authors.forename: Carme
authors.initials: C
authors.lastname: Pelegrí
mesh_terms: D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000096:biosynthesis*; D003292:Convulsants / Q000633:toxicity; D003342:Corpus Striatum / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D004195:Disease Models, Animal; D038362:Glycogen Synthase Kinase 3 / Q000096:biosynthesis*; D000071679:Glycogen Synthase Kinase 3 beta; D007150:Immunohistochemistry; D008297:Male; D009410:Nerve Degeneration / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000378:metabolism; D009574:Nitro Compounds / Q000633:toxicity; D011422:Propionates / Q000633:toxicity; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis*; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis*
chemical_list: D018797:Cell Cycle Proteins; D003292:Convulsants; D004268:DNA-Binding Proteins; D009574:Nitro Compounds; D011422:Propionates; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D064007:Ataxia Telangiectasia Mutated Proteins; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; C015392:3-nitropropionic acid