Bax deficiency promotes an up-regulation of Bim(EL) and Bak during striatal and cortical postnatal development, and after excitotoxic injury

• Published in: Molecular and cellular neuroscience 2008-04, Vol.37 (4), p.663
• Main Authors: Gavaldà, N, Pérez-Navarro, E, García-Martínez, J M, Marco, S, Benito, A, Alberch, J
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; Apoptosis - genetics; Apoptosis Regulatory Proteins - biosynthesis; Apoptosis Regulatory Proteins - genetics; bcl-2 Homologous Antagonist-Killer Protein - biosynthesis; bcl-2 Homologous Antagonist-Killer Protein - genetics; bcl-2-Associated X Protein - deficiency; bcl-2-Associated X Protein - genetics; Bcl-2-Like Protein 11; Cell Death - genetics; Cerebral Cortex - growth & development; Cerebral Cortex - metabolism; Cerebral Cortex - physiology; Corpus Striatum - growth & development; Corpus Striatum - metabolism; Corpus Striatum - physiology; Female; Male; Membrane Proteins - biosynthesis; Membrane Proteins - genetics; Mice; Mice, Inbred C57BL; Mice, Knockout; Proto-Oncogene Proteins - biosynthesis; Proto-Oncogene Proteins - genetics; Quinolinic Acid - toxicity; Up-Regulation - genetics
• ISSN: 1095-9327
• DOI: 10.1016/j.mcn.2007.12.013

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.