Postnatal brain development and neural cell differentiation modulate mitochondrial Bax and BH3 peptide-induced cytochrome c release - PubMed (original) (raw)

Postnatal brain development and neural cell differentiation modulate mitochondrial Bax and BH3 peptide-induced cytochrome c release

B M Polster et al. Cell Death Differ. 2003 Mar.

Abstract

Bax mediates cytochrome c release and apoptosis during neurodevelopment. Brain mitochondria that were isolated from 8-day, 17-day, and adult rats displayed decreasing levels of mitochondrial Bax. The amount of cytochrome c released from brain mitochondria by a peptide containing the BH3 cell death domain decreased with increasing age. However, approximately 60% of cytochrome c in adult brain mitochondria could be released by the BH3 peptide in the presence of exogenous human recombinant Bax. Mitochondrial Bax was downregulated in PC12S neural cells differentiated with nerve growth factor, and mitochondria isolated from these cells demonstrated decreased sensitivity to BH3-peptide-induced cytochrome c release. These results demonstrate that immature brain mitochondria and mitochondria from undifferentiated neural cells are particularly sensitive to cytochrome c release mediated by endogenous Bax and a BH3 death domain peptide. Postnatal developmental changes in mitochondrial Bax levels may contribute to the increased susceptibility of neurons to pathological apoptosis in immature animals.

PubMed Disclaimer

Similar articles

• Bax oligomerization in mitochondrial membranes requires tBid (caspase-8-cleaved Bid) and a mitochondrial protein.
  Roucou X, Montessuit S, Antonsson B, Martinou JC. Roucou X, et al. Biochem J. 2002 Dec 15;368(Pt 3):915-21. doi: 10.1042/BJ20020972. Biochem J. 2002. PMID: 12193163 Free PMC article.
• Smac induces cytochrome c release and apoptosis independently from Bax/Bcl-x(L) in a strictly caspase-3-dependent manner in human carcinoma cells.
  Hasenjäger A, Gillissen B, Müller A, Normand G, Hemmati PG, Schuler M, Dörken B, Daniel PT. Hasenjäger A, et al. Oncogene. 2004 Jun 3;23(26):4523-35. doi: 10.1038/sj.onc.1207594. Oncogene. 2004. PMID: 15064710
• Cellular prion protein inhibits proapoptotic Bax conformational change in human neurons and in breast carcinoma MCF-7 cells.
  Roucou X, Giannopoulos PN, Zhang Y, Jodoin J, Goodyer CG, LeBlanc A. Roucou X, et al. Cell Death Differ. 2005 Jul;12(7):783-95. doi: 10.1038/sj.cdd.4401629. Cell Death Differ. 2005. PMID: 15846375
• BH3-only proteins trigger cytochrome c release, but how?
  Häcker G, Weber A. Häcker G, et al. Arch Biochem Biophys. 2007 Jun 15;462(2):150-5. doi: 10.1016/j.abb.2006.12.022. Epub 2007 Jan 9. Arch Biochem Biophys. 2007. PMID: 17306210 Review.
• Bax, reactive oxygen, and cytochrome c release in neuronal apoptosis.
  Kirkland RA, Franklin JL. Kirkland RA, et al. Antioxid Redox Signal. 2003 Oct;5(5):589-96. doi: 10.1089/152308603770310257. Antioxid Redox Signal. 2003. PMID: 14580315 Review.

Cited by

• Mature neurons: equipped for survival.
  Kole AJ, Annis RP, Deshmukh M. Kole AJ, et al. Cell Death Dis. 2013 Jun 27;4(6):e689. doi: 10.1038/cddis.2013.220. Cell Death Dis. 2013. PMID: 23807218 Free PMC article. Review.
• Bax regulates production of superoxide in both apoptotic and nonapoptotic neurons: role of caspases.
  Kirkland RA, Saavedra GM, Cummings BS, Franklin JL. Kirkland RA, et al. J Neurosci. 2010 Dec 1;30(48):16114-27. doi: 10.1523/JNEUROSCI.2862-10.2010. J Neurosci. 2010. PMID: 21123558 Free PMC article.
• Alpha II Spectrin breakdown products in immature Sprague Dawley rat hippocampus and cortex after traumatic brain injury.
  Schober ME, Requena DF, Davis LJ, Metzger RR, Bennett KS, Morita D, Niedzwecki C, Yang Z, Wang KK. Schober ME, et al. Brain Res. 2014 Jul 29;1574:105-12. doi: 10.1016/j.brainres.2014.05.046. Epub 2014 Jun 12. Brain Res. 2014. PMID: 24929209 Free PMC article.
• Auto-activation of the apoptosis protein Bax increases mitochondrial membrane permeability and is inhibited by Bcl-2.
  Tan C, Dlugosz PJ, Peng J, Zhang Z, Lapolla SM, Plafker SM, Andrews DW, Lin J. Tan C, et al. J Biol Chem. 2006 May 26;281(21):14764-75. doi: 10.1074/jbc.M602374200. Epub 2006 Mar 29. J Biol Chem. 2006. PMID: 16571718 Free PMC article.
• Postnatal developmental regulation of Bcl-2 family proteins in brain mitochondria.
  Soane L, Siegel ZT, Schuh RA, Fiskum G. Soane L, et al. J Neurosci Res. 2008 May 1;86(6):1267-76. doi: 10.1002/jnr.21584. J Neurosci Res. 2008. PMID: 18058945 Free PMC article.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Nature Publishing Group

• Other Literature Sources

  • The Lens - Patent Citations Database

• Molecular Biology Databases

  • GlyGen glycoinformatics resource

• Research Materials

  • NCI CPTC Antibody Characterization Program