Skip to main content
SpringerLink
Log in

bcl2, bax and nestin in the brains of patients with neurodegeneration and those of normal aging

  • Original Article
  • Published:
Journal of Molecular Neuroscience Aims and scope Submit manuscript

Abstract

This study was conducted by employing specimens from the frontal cortices of Alzheimer, multiple-infarct dementia patients, and those of normal aging (age matched to patients). The objective was to evaluate and compare the bcl2, bax, and nestin patterns in these three groups. Using immunocytochemistry, it was observed that bcl2 and bax active sites were colocalized in 45% of cells in Alzheimer, 52% of cells in multiple infarct, and 30% of cells in normal aging. bcl2 and bax could also be separately located in cells of all three groups. bax cells were most prominent in number in Alzheimer patients and least prominent in normal aging. nestin was found in all three groups but was most prominent in the multiple-infarct patients. Both astrocytes and neurons demonstrated positive nestin sites. The difference in pattern between groups will lead to further understanding of cellular changes in neurodegenerative patients and those of normal aging.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Adams J. M. and Cory S. (1998) The Bcl-2 protein family: arbiters of cell survival. Science 281, 1322–1326.

    Article  PubMed  CAS  Google Scholar 

  • Alberi S., Raggenbass M., de Bilbao F., and Dubois-Dauphin M. (1996) Axotomized neonatal motoneurons overexpressing the bcl2 proto-oncogene retain functional electrophysiological properties. Proc. Natl. Acad. Sci. U. S. A. 93, 3978–3983.

    Article  Google Scholar 

  • Bruggers C. S., Fults D., Perkins S. L., Coffin C. M., and Carroll W. L. (1999) Coexpression of genes involved in apoptosis in central nervous system neoplasms. J. Pediatr. Hematol. Oncol. 21, 19–25.

    Article  PubMed  CAS  Google Scholar 

  • Cao Y. J., Shibata T., and Rainov N. G. (2002) Liposome-mediated transfer of the bcl-2 gene results in neuroprotection after in vivo transient focal cerebral ischemia in an animal model. Gene Ther. 9, 415–419.

    Article  PubMed  CAS  Google Scholar 

  • Carrio R., Lopez-Hoyos M., Jimeno J., Benedict M. A., Merino R., Benito A., Fernandez-Luna J. L., et al. (1996) A1 demonstrates restricted tissue distribution during embryonic development and functions to protect against cell death. Am. J. Pathol. 149, 2133–2142.

    Google Scholar 

  • Chen S., Pickard J. D., and Harris N. G. (2003) Time course of cellular pathology after controlled cortical impact injury. Exp. Neurol. 182, 87–102.

    Article  PubMed  CAS  Google Scholar 

  • Chong M. J., Murray M. R., Gosink E. C., Russell H. R., Srinivasan A., Kapsetaki M., et al. (2000) Atm and Bax cooperate in ionizing radiation-induced apoptosis in the central nervous system. Proc. Natl. Acad. Sci. U. S. A. 97, 889–894.

    Article  PubMed  CAS  Google Scholar 

  • Colucci-D’Amato G. L., Tino A., Pernas-Alonso R., ffrench-Mullen J. M., and di Porzio U. (1999) Neuronal and glial properties coexist in a novel mouse CNS immortalized cell line. Exp. Cell Res. 252, 383–391.

    Article  PubMed  CAS  Google Scholar 

  • D’Sa-Eipper C., Leonard J. R., Putcha G., Zheng T. S., Flavell R. A., Rakic P., et al. (2001) DNA damage-induced neural precursor cell apoptosis requires p53 and caspase 9 but neither Bax nor caspase 3. Development 28, 137–146.

    Google Scholar 

  • Duggal N., Schmidt-Kastner R., and Hakim A. M. (1997) Nestin expression in reactive astrocytes following focal cerebral ischemia in rats. Brain Res. 768, 1–9.

    Article  PubMed  CAS  Google Scholar 

  • Engidawork E., Gulesserian T., Seidl R., Cairns N., and Lubec G. (2001) Expression of apoptosis related proteins in brains of patients with Alzheimer’s disease. Neurosci. Lett. 303, 79–82.

    Article  PubMed  CAS  Google Scholar 

  • Ferrer I. and Planas A. M. (2003) Signaling of cell death and cell survival following focal cerebral ischemia: life and death struggle in the penumbra. J. Neuropathol. Exp. Neurol. 62, 329–339.

    PubMed  Google Scholar 

  • Guo B., Zhai D., Cabezas E., Welsh K., Nouraini S., Satterthwait A. C. and Reed J. C. (2003) Humanin peptide suppresses apoptosis by interfering with Bax activation. Nature 423, 456–461.

    Article  PubMed  CAS  Google Scholar 

  • Holmin S., von Gertten C., Sandberg-Nordqvist A. C., Lendahl U., and Mathiesen T. (2001) Induction of astrocytic nestin expression by depolarization in rats. Neurosci. Lett. 314, 151–155.

    Article  PubMed  CAS  Google Scholar 

  • Jellinger K. A. (2000) Cell death mechanisms in Parkinson disease. J. Neural Transm. 107, 1–29.

    Article  PubMed  CAS  Google Scholar 

  • Kakazu A., Chandrasekher G., and Bazan H. E. (2004) HGF protects corneal epithelial cells from apoptosis by the PI-3K/Akt-1/Bad- but not the ERK1/2-mediated signaling pathway. Invest. Ophthalmol. Vis. Sci. 45, 3485–3492.

    Article  PubMed  Google Scholar 

  • Kroemer G. (1997) The proto-oncogene Bcl-2 and its role in regulating apoptosis. Nat. Med. 3, 614–620.

    Article  PubMed  CAS  Google Scholar 

  • Li W. P., Chan W. Y., Lai H. W. L., and Yew D. T. (1997) Terminal dUTP nick end labelling (TUNEL) positive cells in different regions of the brain in normal aging and Alzheimer patients. J. Mol. Neurosci. 8, 75–82.

    Article  PubMed  CAS  Google Scholar 

  • Liu D., Lu C., Wan R., Auyeung W. W., and Mattson M. P. (2002) Activation of mitochondrial ATP-dependent potassium channels protects neurons against ischemia-induced death by a mechanism involving suppression of Bax translocation and cytochrome c release. J. Cereb. Blood Flow Metab. 22, 431–443.

    Article  PubMed  CAS  Google Scholar 

  • Lu J., Moochhala S., Kaur C., and Ling E. (2000) Changes in apoptosis-related protein (p53, Bax, Bcl-2 and Fos) expression with DNA fragmentation in the central nervous system in rats after closed head injury. Neurosci. Lett. 290, 89–92.

    Article  PubMed  CAS  Google Scholar 

  • Martinez-Arribas F., Nunez-Villar M. J., Lucas A. R., Sanchez J., Tejerina A., and Schneider J. (2003) Immunofluorometric study of Bcl-2 and Bax expression in clinical fresh tumor samples from breast cancer patients. Anticancer Res. 23, 565–568.

    PubMed  CAS  Google Scholar 

  • Mazurek U., Bierzynska-Macyszyn G., Gola J., Orchel J., Slowinski J., and Wilczok T. (2001) BCL2 and BAX mRNA concentration profile in fibrillary astrocytoma. Folia Histochem. Cytobiol. 39, 179–180.

    PubMed  Google Scholar 

  • Meltzer H., Hatton J. D., and Sang U. H. (1998) Cell type-specific development of rodent central nervous system progenitor cells in culture. J. Neurosurg. 88, 93–98.

    Article  PubMed  CAS  Google Scholar 

  • Middleton G., Wyatt S., Ninkina N., and Davies A. M. (2001) Reciprocal developmental changes in the roles of Bcl-w and Bcl-x (L) in regulating sensory neuron survival. Development 128, 447–457.

    PubMed  CAS  Google Scholar 

  • Mizuno Y., Takeuchi T., Takatama M., and Okamoto K. (2003) Expression of nestin in Purkinje cells in patients with Creutzfeldt-Jakob disease. Neurosci. Lett. 352, 109–112.

    Article  PubMed  CAS  Google Scholar 

  • Oltvai Z. N., Milliman C. L., and Korsmeyer S. J. (1993) Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell 74, 609–619.

    Article  PubMed  CAS  Google Scholar 

  • Osterhout D. J., Marin-Husstege M., Abano P., and Casaccia-Bonnefil P. (2002) Molecular mechanisms of enhanced susceptibility to apoptosis in differentiating oligodendrocytes. J. Neurosci. Res. 69, 24–29.

    Article  PubMed  CAS  Google Scholar 

  • Ray S. K., Wilford G. G., Crosby C. V., Hogan E. L., and Banik N. L. (1999) Diverse stimuli induce calpain overexpression and apoptosis in C6 glioma cells. Brain Res. 829, 18–27.

    Article  PubMed  CAS  Google Scholar 

  • Rice A. C., Khaldi A., Harvey H. B., Salman N. J., White F., Fillmore H., and Bullock M. R. (2003) Proliferation and neuronal differentiation of mitotically active cells following traumatic brain injury. Exp. Neurol. 183, 406–417.

    Article  PubMed  CAS  Google Scholar 

  • Sahlgren C. M., Mikhailov A., Hellman J., Chou Y. H., Lendahl U., Goldman R. D., and Eriksson J. E. (2001) Mitotic reorganization of the intermediate filament protein nestin involves phosphorylation by cdc2 kinase. J. Biol. Chem. 276, 16456–16463.

    Article  PubMed  CAS  Google Scholar 

  • Seo S. Y., Chen Y. B., Ivanovska I., Ranger A. M., Hong S. J., Dawson V. L., et al. (2004) BAD is a pro-survival factor prior to activation of its pro-apoptotic function. J Biol. Chem. 279, 42240–42249.

    Article  PubMed  CAS  Google Scholar 

  • Siskas N., Lefkopoulos A., Ioannidis I., Charitandi A., and Dimitriadis A. S. (2003) Cortical laminar necrosis in brain infarct: serial MRI. Neuroradiology 45, 283–288.

    PubMed  CAS  Google Scholar 

  • Sugawara K., Kurihara H., Negishi M., Saito N., Nakazato Y., Sasaki T., and Takeuchi T. (2002) Nestin as a marker for proliferative endothelium in gliomas. Lab. Invest. 82, 345–351.

    PubMed  CAS  Google Scholar 

  • Tanaka T., Hanafusa N., Ingelfinger J. R., Ohse T., Fujita T., and Nangaku M. (2003) Hypoxia induces apoptosis in SV40-immortalized rat proximal tubular cells through the mitochondrial pathways, devoid of HIF1-mediated upregulation of Bax. Biochem. Biophys. Res. Commun. 309, 222–231.

    Article  PubMed  CAS  Google Scholar 

  • Tonchev A. B., Yamashima T., Zhao L., Okano H. J., and Okano H. (2003) Proliferation of neural and neuronal progenitors after global brain ischemia in young adult macaque monkeys. Mol. Cell. Neurosci. 23, 292–301.

    Article  PubMed  CAS  Google Scholar 

  • Wei L. C., Shi M., Chen L. W., Cao R., Zhang P., and Chan Y. S. (2002) Nestin-containing cells express glial fibrillary acidic protein in the proliferative regions of central nervous system of postnatal developing and adult mice. Brain Res. Dev. Brain Res. 139, 9–17.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Anatomy, Chinese University of Hong Kong, Shatin, N.T., Hong Kong

    Gang Lu, W. H. Kwong, Qi Li & David T. Yew

  2. Kunming Medical College, Kunming, Yunan, China

    Gang Lu, W. H. Kwong, Xicai Wang & Zhongtang Feng

Authors
  1. Gang Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. W. H. Kwong
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Qi Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xicai Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zhongtang Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. David T. Yew
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David T. Yew.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lu, G., Kwong, W.H., Li, Q. et al. bcl2, bax and nestin in the brains of patients with neurodegeneration and those of normal aging. J Mol Neurosci 27, 167–174 (2005). https://doi.org/10.1385/JMN:27:2:167

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1385/JMN:27:2:167

Index Entries

Search

Navigation