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

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) 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 (35) Citing Articles via Google Scholar Google Scholar Articles by Zaidi, A. U. Articles by Roth, K. A. Search for Related Content PubMed PubMed Citation Articles by Zaidi, A. U. Articles by Roth, K. A.

 Previous Article  |  Next Article 

The Journal of Neuroscience, January 1, 2001, 21(1):169-175

Bcl-X_L-Caspase-9 Interactions in the Developing Nervous System: Evidence for Multiple Death Pathways

Aliya U. Zaidi¹, Cleta D'Sa-Eipper¹, Jennifer Brenner¹, Keisuke Kuida², Timothy S. Zheng³, Richard A. Flavell⁴, Pasko Rakic⁵, and Kevin A. Roth¹

¹ Department of Pathology and Immunology, Division of Neuropathology, Washington University School of Medicine, St. Louis, Missouri 63110, ² Vertex Pharmaceuticals, Cambridge, Massachusetts 02139-4242, ³ Department of Inflammation, Immunology, and Cell Biology, Biogen, Cambridge, Massachusetts 02142, and Departments of ⁴ Immunology, and ⁵ Neurobiology, Yale University School of Medicine New Haven, Connecticut 06520-8011

Programmed cell death is critical for normal nervous system development and is regulated by Bcl-2 and Caspase family members. Targeted disruption of bcl-x_L, an antiapoptotic bcl-2 gene family member, causes massive death of immature neurons in the developing nervous system whereas disruption of caspase-9, a proapoptotic caspase gene family member, leads to decreased neuronal apoptosis and neurodevelopmental abnormalities. To determine whether Bcl-X_L and Caspase-9 interact in an obligate pathway of neuronal apoptosis, bcl-x/caspase-9 double homozygous mutants were generated. The increased apoptosis of immature neurons observed in Bcl-X_L-deficient embryos was completely prevented by concomitant Caspase-9 deficiency. In contrast, bcl-x^//caspase-9^/ embryonic mice exhibited an expanded ventricular zone and neuronal malformations identical to that observed in mice lacking only Caspase-9. These results indicate both epistatic and independent actions of Bcl-X_L and Caspase-9 in neuronal programmed cell death.

To examine Bcl-2 and Caspase family-dependent apoptotic pathways in telencephalic neurons, we compared the effects of cytosine arabinoside (AraC), a known neuronal apoptosis inducer, on wild-type, Bcl-X_L-, Bax-, Caspase-9-, Caspase-3-, and p53-deficient telencephalic neurons in vitro. AraC caused extensive apoptosis of wild-type and Bcl-X_L-deficient neurons. p53- and Bax-deficient neurons showed marked protection from AraC-induced death, whereas Caspase-9- and Caspase-3-deficient neurons showed minimal or no protection, respectively. These findings contrast with our previous investigation of AraC-induced apoptosis of telencephalic neural precursor cells in which death was completely blocked by p53 or Caspase-9 deficiency but not Bax deficiency. In total, these results indicate a transition from Caspase-9- to Bax- and Bcl-X_L-mediated neuronal apoptosis.

Key words: development; programmed cell death; p53; apoptosis; Bax; Caspase-3

---

Copyright © 2001 Society for Neuroscience  0270-6474/01/211169-07$05.00/0

This article has been cited by other articles:

				R. S. Akhtar, B. J. Klocke, A. Strasser, and K. A. Roth Loss of BH3-only Protein Bim Inhibits Apoptosis of Hemopoietic Cells in the Fetal Liver and Male Germ Cells but Not Neuronal Cells in Bcl-x-deficient Mice J. Histochem. Cytochem., October 1, 2008; 56(10): 921 - 927. [Abstract] [Full Text] [PDF]

				M.-Y. Chang, W. Sun, W. Ochiai, K. Nakashima, S.-Y. Kim, C.-H. Park, J. S. Kang, J.-W. Shim, A-Y. Jo, C.-S. Kang, et al. Bcl-XL/Bax Proteins Direct the Fate of Embryonic Cortical Precursor Cells Mol. Cell. Biol., June 15, 2007; 27(12): 4293 - 4305. [Abstract] [Full Text] [PDF]

				Y. Tao, D. Yan, Q. Yang, R. Zeng, and Y. Wang Low K+ Promotes NF-{kappa}B/DNA Binding in Neuronal Apoptosis Induced by K+ Loss Mol. Cell. Biol., February 1, 2006; 26(3): 1038 - 1050. [Abstract] [Full Text] [PDF]

				S. Vyas, P. Juin, D. Hancock, Y. Suzuki, R. Takahashi, A. Triller, and G. Evan Differentiation-dependent Sensitivity to Apoptogenic Factors in PC12 Cells J. Biol. Chem., July 23, 2004; 279(30): 30983 - 30993. [Abstract] [Full Text] [PDF]

				H. Vaghefi, A. L. Hughes, and K. E. Neet Nerve Growth Factor Withdrawal-mediated Apoptosis in Naive and Differentiated PC12 Cells through p53/Caspase-3-dependent and -independent Pathways J. Biol. Chem., April 9, 2004; 279(15): 15604 - 15614. [Abstract] [Full Text] [PDF]

				L.-Y. Yu, E. Jokitalo, Y.-F. Sun, P. Mehlen, D. Lindholm, M. Saarma, and U. Arumae GDNF-deprived sympathetic neurons die via a novel nonmitochondrial pathway J. Cell Biol., December 8, 2003; 163(5): 987 - 997. [Abstract] [Full Text] [PDF]

				R. W. Oppenheim, R. A. Flavell, S. Vinsant, D. Prevette, C.-Y. Kuan, and P. Rakic Programmed Cell Death of Developing Mammalian Neurons after Genetic Deletion of Caspases J. Neurosci., July 1, 2001; 21(13): 4752 - 4760. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help