QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, April 14, 2004, 24(15):3721-3725; doi:10.1523/JNEUROSCI.5101-03.2004

This Article Full Text Full Text (PDF) A correction has been published Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (26) Citing Articles via Google Scholar Google Scholar Articles by Imaizumi, K. Articles by Nuñez, G. Search for Related Content PubMed PubMed Citation Articles by Imaizumi, K. Articles by Nuñez, G.

 Previous Article  |  Next Article 

BRIEF COMMUNICATION
Critical Role for DP5/Harakiri, a Bcl-2 Homology Domain 3-Only Bcl-2 Family Member, in Axotomy-Induced Neuronal Cell Death

Kazunori Imaizumi,^1 * Adalberto Benito,^2 * Sumiko Kiryu-Seo,^3 * Victor Gonzalez,² Naohiro Inohara,² Andrew P. Leiberman,² Hiroshi Kiyama,² and Gabriel Nuñez²

¹Division of Structural Cellular Biology, Nara Institute of Science and Technology, Nara 630-0101, Japan, ²Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan 48109, and ³Department of Anatomy and Neurobiology, Graduate School of Medicine, Osaka City University, Osaka 545-8585, Japan

The survival of neurons is maintained primarily by neurotrophic factors that suppress the apoptotic program. Axotomy or removal of peripheral targets causes neuronal cell death, but the mechanisms involved in the induction of this type of cell death remain poorly understood. Here, we show that DP5/Harakiri, a Bcl-2 homology domain 3-only member of the Bcl-2 family, is induced in motoneurons after transection of the hypoglossal nerve in mice and in sympathetic neurons after nerve growth factor (NGF) withdrawal. To assess the role of DP5 in neuronal cell death, mutant mice deficient in DP5 were generated by gene targeting. DP5^–/– mice were viable and exhibited normal postnatal development. Notably, motoneurons from DP5^–/– mice were highly protected from cell death induced by resection of the hypoglossal nerve compared with motoneurons from DP5^+/+ littermate mice. In addition, deficiency of DP5 in superior cervical ganglia (SCG) neurons resulted in delayed neuronal cell death triggered by NGF withdrawal. Analysis of SCG neurons from DP5^–/– mice revealed increased preservation of mitochondrial membrane potential and reduced activation of caspase-3 compared with neurons from wild-type mice. These results indicate that DP5 plays an important role in neuronal cell death induced by axotomy and NGF deprivation through the regulation of mitochondrial function and caspase-3 activation.

Key words: BH3-only; Bcl-2; DP5; HRK; neuronal cell death; NGF

---

Received Nov 18, 2003; revised February 26, 2004; accepted February 27, 2004.

This article has been cited by other articles:

				S. F. Fischer, P. Bouillet, K. O'Donnell, A. Light, D. M. Tarlinton, and A. Strasser Proapoptotic BH3-only protein Bim is essential for developmentally programmed death of germinal center-derived memory B cells and antibody-forming cells Blood, December 1, 2007; 110(12): 3978 - 3984. [Abstract] [Full Text] [PDF]

				L. Coultas, S. Terzano, T. Thomas, A. Voss, K. Reid, E. G. Stanley, C. L. Scott, P. Bouillet, P. Bartlett, J. Ham, et al. Hrk/DP5 contributes to the apoptosis of select neuronal populations but is dispensable for haematopoietic cell apoptosis J. Cell Sci., June 15, 2007; 120(12): 2044 - 2052. [Abstract] [Full Text] [PDF]

				G. M. Kalinec, M. E. Fernandez-Zapico, R. Urrutia, N. Esteban-Cruciani, S. Chen, and F. Kalinec Pivotal role of Harakiri in the induction and prevention of gentamicin-induced hearing loss PNAS, November 1, 2005; 102(44): 16019 - 16024. [Abstract] [Full Text] [PDF]

				H. K. Wong, M. Fricker, A. Wyttenbach, A. Villunger, E. M. Michalak, A. Strasser, and A. M. Tolkovsky Mutually Exclusive Subsets of BH3-Only Proteins Are Activated by the p53 and c-Jun N-Terminal Kinase/c-Jun Signaling Pathways during Cortical Neuron Apoptosis Induced by Arsenite Mol. Cell. Biol., October 1, 2005; 25(19): 8732 - 8747. [Abstract] [Full Text] [PDF]

				C. G. Besirli, E. F. Wagner, and E. M. Johnson Jr. The limited role of NH2-terminal c-Jun phosphorylation in neuronal apoptosis: Identification of the nuclear pore complex as a potential target of the JNK pathway J. Cell Biol., August 1, 2005; 170(3): 401 - 411. [Abstract] [Full Text] [PDF]

				S. Desagher, D. Severac, A. Lipkin, C. Bernis, W. Ritchie, A. Le Digarcher, and L. Journot Genes Regulated in Neurons Undergoing Transcription-dependent Apoptosis Belong to Signaling Pathways Rather than the Apoptotic Machinery J. Biol. Chem., February 18, 2005; 280(7): 5693 - 5702. [Abstract] [Full Text] [PDF]

				S. Kiryu-Seo, T. Hirayama, R. Kato, and H. Kiyama Noxa Is a Critical Mediator of p53-Dependent Motor Neuron Death after Nerve Injury in Adult Mouse J. Neurosci., February 9, 2005; 25(6): 1442 - 1447. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help