Skip to main content
SpringerLink
Log in

Neuronal Apoptosis: BH3-Only Proteins the Real Killers?

  • Published:
Journal of Bioenergetics and Biomembranes Aims and scope Submit manuscript

Abstract

At present there is a poor understanding of the events that lead up to neuronal apoptosis that occurs in neurodegenerative diseases and following acute ischemic episodes. Apoptosis is critical for the elimination of unwanted neurons within the developing nervous system. The Bcl-2 family of proteins contains pro- and anti-apoptotic proteins that regulate the mitochondrial pathway of apoptosis. There is increasing interest in a subfamily of the Bcl-2 family, the BH3-only proteins, and their pro-apoptotic effects within neurons. Recently ischemic and seizure-induced neuronal injury has been shown to result in the activation of the BH3-only protein, Bid. This protein is cleaved and the truncated protein (tBid) translocates to the mitochondria. The translocation of tBid to the mitochondria is associated with the activation of outer mitochondrial membrane proteins Bax/Bak and the release of cytochrome C from the mitochondria. ER stress also has been implicated as a factor for the induction of apoptosis in ischemic neuronal injury. The induction of ER stress in hippocampal neurons has been shown to activate expression of bb3/PUMA, a member of the BH3-only gene family. Activation of PUMA is associated with the activation and clustering of the pro-apoptotic Bcl-2 family member Bax and the loss of cytochrome C from the mitochondria.

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.

Similar content being viewed by others

REFERENCES

  • Ankarcrona, M., Dypbukt, J. M., Bonfoco, E., Zhivotovsky, B., Orrenius, S., Lipton, S. A., and Nicotera, P. (1995). Neuron 15, 961–973.

    PubMed  Google Scholar 

  • Annis, M. G., Zamzami, N., Zhu, W., Penn, L. Z., Kroemer, G., Leber, B., and Andrews, D. W. (2001). Oncogene 20, 1939–1952.

    PubMed  Google Scholar 

  • Aoyagi, M., Higashino, F., Yasuda, M., Takahashi, A., Sawada, Y., Totsuka, Y., Kohgo, T., and Sano, H. (2003). Oncogene 22, 6919–6927.

    PubMed  Google Scholar 

  • Armstrong, R. C., Aja, T. J., Hoang, K. D., Gaur, S., Bai, X., Alnemri, E. S., Litwack, G., Karanewsky, D. S., Fritz, L. C., and Tomaselli, K. J. (1997). J. Neurosci. 17, 553–562.

    PubMed  Google Scholar 

  • Biswas, S. C., and Greene, L. A. (2002). J. Biol. Chem. 277, 49511–49516.

    PubMed  Google Scholar 

  • Budd, S. L., Tenneti, L., Lishnak, T., and Lipton, S. A. (2000). Proc. Natl. Acad. Sci. U.S.A. 97, 6161–6166.

    PubMed  Google Scholar 

  • Chen, M., He, H., Zhan, S., Krajewski, S., Reed, J. C., and Gottlieb, R. A. (2001). J. Biol. Chem. 276, 30724–30728.

    PubMed  Google Scholar 

  • Choi, D. W. (1994). Ann. N.Y. Acad. Sci. 747, 162–171.

    PubMed  Google Scholar 

  • Choi, D. W. (1987). J. Neurosci. 7, 369–379.

    PubMed  Google Scholar 

  • Conradt, B., and Horvitz, H. R. (1998). Cell 93, 519–529.

    PubMed  Google Scholar 

  • Desagher, S., and Martinou, J. C. (2000). Trends Cell Biol. 10, 369–377.

    PubMed  Google Scholar 

  • Desagher, S., Osen-Sand, A., Nichols, A., Eskes, R., Montessuit, S., Lauper, S., Maundrell, K., Antonsson, B., and Martinou, J. C. (1999). J. Cell Biol. 144, 891–901.

    PubMed  Google Scholar 

  • Eskes, R., Desagher, S., Antonsson, B., and Martinou, J. C. (2000). Mol. Cell Biol. 20, 929–935.

    PubMed  Google Scholar 

  • Eskes, R., Antonsson, B., Osen-Sand, A., Montessuit, S., Richter, C., Sadoul, R., Mazzei, G., Nichols, A., and Martinou, J. C. (1998). J. Cell Biol. 143, 217–224.

    PubMed  Google Scholar 

  • Goping, I. S., Gross, A., Lavole, J. N., Nguyen, M., Jemmerson, R., Roth, K., Korsmeyer, S. J., and Shore, G. C. (1998) J. Cell Biol. 143, 207–215.

    PubMed  Google Scholar 

  • Hacki, J., Egger, L., Monney, L., Conus, S., Rosse, T., Fellay, I., and Borner, C. (2000). Oncogene 19, 2286–2295.

    PubMed  Google Scholar 

  • Hegde, R., Srinivasula, S. M., Ahmad, M., Fernandes-Alnemri, T., and Alnemri, E. S. (1998). J. Biol. Chem. 273, 7783–7786.

    PubMed  Google Scholar 

  • Henshall, D. C., Bonislawski, D. P., Skradski, S. L., Lan, J. Q., Meller, R., and Simon RP. (2001). Neurobiol. Dis. 8, 568–580.

    PubMed  Google Scholar 

  • Nakagawa, T., and Yuan, J. (2000). J. Cell Biol. 150, 887–894.

    PubMed  Google Scholar 

  • Nakagawa, T., Zhu, H., Morishima, N., Li, E., Xu, J., Yankner, B. A., and Yuan, J. (2000). Nature 403,98–103.

    PubMed  Google Scholar 

  • Huang, D. C., and Strasser, A. (2000). Cell 103, 839–842.

    PubMed  Google Scholar 

  • Inohara, N., Ding, L., Chen, S., and Nunez, G. (1997). EMBO J. 16, 1686–1694.

    PubMed  Google Scholar 

  • Kaufman, R. J. (1999). Genes Dev. 13, 1211–1233.

    PubMed  Google Scholar 

  • Kuwana, T., Mackey, M. R., Perkins, G., Ellisman, M. H., Latterich, M., Schneiter, R., Green, D. R., and Newmeyer, D. D. (2002). Cell 111, 331–342.

    PubMed  Google Scholar 

  • Lankiewicz, S., Marc Luetjens, C., Truc Bui, N., Krohn, A. J., Poppe, M., Cole, G. M., Saido, T. C., and Prehn, J. H. (2000). J. Biol. Chem. 275, 17064–17071.

    PubMed  Google Scholar 

  • Li, H., Zhu, H., Xu, C. J., and Yuan, J. (1998). Cell 94, 491–501.

    PubMed  Google Scholar 

  • Luetjens, C. M., Bui, N. T., Sengpiet, B., Munstermann, G., Poppe, M., Krohn, A. J., Bauerbach, E., Krieglstein, J., and Prehn, J. H. J. Neurosci. 20, 5715–5723.

  • Luo, X., Budihardjo, I., Zou, H., Slaughter, C., and Wang, X. (1998). Cell 94, 481–490.

    PubMed  Google Scholar 

  • Mund, T., Gewies, A., Schoenfeld, N., Bauer, M. K., and Grimm, S. (2003). FASEB J. 17, 696–698.

    PubMed  Google Scholar 

  • Oda, E., Ohki, R., Murasawa, H., Nemoto, J., Shibue, T., Yamashita, T., Tokino, T., Taniguchi, T., and Tanaka, N. (2000). Science 288, 1053–1058.

    PubMed  Google Scholar 

  • Paschen, W., and Frandsen, A. (2001). J. Neurochem. 79, 719–725.

    PubMed  Google Scholar 

  • Perez-Sala, D., and Mollinedo, F. (1995). J. Cell Physiol. 163, 523–531.

    PubMed  Google Scholar 

  • Plesnila, N., Zinkel, S., Le, D. A., Amin-Hanjani, S., Wu, Y., Qiu, J., Chiarugi, A., Thomas, S. S., Kohane, D. S., Korsmeyer, S. J., and Moskowitz, M. A. (2001). Proc. Natl. Acad. Sci. U.S.A. 98, 15318–15323.

    PubMed  Google Scholar 

  • Putcha, G. V., Moulder, K. L., Golden, J. P., Bouillet, P., Adams, J. A., Strasser, A., and Johnson, E. M. (2001). Neuron 29, 615–628.

    PubMed  Google Scholar 

  • Puthalakath, H., Villunger, A., O'Reilly, L. A., Beaumont, J. G., Coultas, L., Cheney, R. E., Huang, D. C., and Strasser, A. (2001). Science 293, 1829–1832.

    PubMed  Google Scholar 

  • Puthalakath, H., Huang, D. C., O'Reilly, L. A., King, S. M., and Strasser, A. (1999). Mol. Cell. 3, 287–296.

    PubMed  Google Scholar 

  • Reimertz, C., Kogel, D., Rami, A., Chittenden, T., and Prehn, J. H. (2003). J. Cell Biol. 162, 587–597.

    PubMed  Google Scholar 

  • Shinoda, S., Schindler, C. K., Meller, R., Lan, J. Q., So, N., Taki, W., Simon, R. P., and Henshall, D. C. (2004). J. Clin. Invest. 113, 1059–1068.

    PubMed  Google Scholar 

  • Stoka, V., Turk, B., Schendel, S. L., Kim, T. H., Cirman, T., Snipas, S. J., Ellerby, L. M., Bredesen, D., Freeze, H., Abrahamson, M., Bromme, D., Krajewski, S., Reed, J. C., Yin, X. M., Turk, V., and Salvesen, G. S. (2001). J. Biol. Chem. 276, 3149–3157.

    PubMed  Google Scholar 

  • Tymianski, M., Charlton, M. P., Carlen, P. L., and Tator, C. H. (1993). Brain Res. 607,19–23.

    Google Scholar 

  • Ward, M. W., Rego, A. C., Frenguelli, B. G., and Nicholls, D. G. (2000). J. Neurosci. 20, 7208–7219

    PubMed  Google Scholar 

  • Wei, M. C., Zong, W. X., Cheng, E. H., Lindsten, T., Panoutsakopoulou, V., Ross, A. J., Roth, K. A., MacGregor, G. R., Thompson, C. B., and Korsmeyer, S. J. (2001). Science 292, 727–730.

    PubMed  Google Scholar 

  • Wei, M. C., Lindsten, T., Mootha, V. K., Weiler, S., Gross, A., Ashiya, M., Thompson, C. B., and Korsmeyer, S. J. (2000). Genes Dev. 14, 2060–2071.

    PubMed  Google Scholar 

  • Yasuda, M., Theodorakis, P., Subramanian, T., and Chinnadurai, G. (1998). J. Biol. Chem. 273, 12415–12421.

    PubMed  Google Scholar 

  • Yu, J., Zhang, L., Hwang, P. M., Kinzler, K. W., and Vogelstein, B. (2001). Mol. Cell. 7, 673–682.

    PubMed  Google Scholar 

  • Zha, H., Aime-Sempe, C., Sato, T., and Reed, J. C. (1996). J. Biol. Chem. 271, 7440–7444.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Physiology, Royal College of Surgeons, 123 St Stephen's, Green, Dublin 2, Ireland

    Manus W. Ward & Jochen H. M. Prehn

  2. Experimental Neurosurgery, Johann Wolfgang Goethe University Clinics, 60590, Frankfurt, Germany

    Donat Kögel

Authors
  1. Manus W. Ward
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Donat Kögel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jochen H. M. Prehn
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ward, M.W., Kögel, D. & Prehn, J.H.M. Neuronal Apoptosis: BH3-Only Proteins the Real Killers?. J Bioenerg Biomembr 36, 295–298 (2004). https://doi.org/10.1023/B:JOBB.0000041756.23918.11

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/B:JOBB.0000041756.23918.11

Search

Navigation