title: Bax deficiency promotes an up-regulation of Bim(EL) and Bak during striatal and cortical postnatal development, and after excitotoxic injury.
abstract: In this study we analyzed whether other members of the Bcl-2 family are regulated in the absence of Bax during the postnatal development of the striatum and cortex and after striatal excitotoxic lesion. Compared with wild-type animals, Bax knockout mice showed region- and time-dependent increases in pro-apoptotic proteins Bak and Bim(EL). Excitotoxicity induced in the adult striatum increased Bim(EL) in both genotypes whereas Bak and Bcl-x(L) were only increased in Bax knockout mice. However, translocation of Bim(EL) protein to the mitochondrial fraction, cytochrome c release and caspase-3 activation were only observed in wild-type striata. Furthermore, analysis of Bim null mutant mice showed that this protein is not essential to excitotoxicity-induced striatal cell death. In conclusion, our results show that in Bax deficient mice Bim(EL) and Bak are specifically regulated during postnatal development, suggesting that these proteins may participate in the compensatory mechanisms triggered in the absence of Bax. In contrast, Bax is required to induce apoptosis after excitotoxicity in the adult striatum.
authors.affiliation: Departament de Biologia Cel-lular i Anatomia Patològica, Universitat de Barcelona, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
authors.forename: N
authors.initials: N
authors.lastname: Gavaldà
authors.forename: E
authors.initials: E
authors.lastname: Pérez-Navarro
authors.forename: J M
authors.initials: JM
authors.lastname: García-Martínez
authors.forename: S
authors.initials: S
authors.lastname: Marco
authors.forename: A
authors.initials: A
authors.lastname: Benito
authors.forename: J
authors.initials: J
authors.lastname: Alberch
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis* / Q000235:genetics; D000072224:Bcl-2-Like Protein 11; D016923:Cell Death / Q000235:genetics; D002540:Cerebral Cortex / Q000254:growth & development / Q000378:metabolism* / Q000502:physiology; D003342:Corpus Striatum / Q000254:growth & development / Q000378:metabolism* / Q000502:physiology; D005260:Female; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D017378:Quinolinic Acid / Q000633:toxicity; D015854:Up-Regulation / Q000235:genetics; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000096:biosynthesis* / Q000235:genetics; D051028:bcl-2-Associated X Protein / Q000172:deficiency* / Q000235:genetics
chemical_list: D051017:Apoptosis Regulatory Proteins; C494773:Bak1 protein, mouse; C494827:Bax protein, mouse; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D017378:Quinolinic Acid