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 (60) Citing Articles via Google Scholar Google Scholar Articles by Chen, R.-W. Articles by Chuang, D.-M. Search for Related Content PubMed PubMed Citation Articles by Chen, R.-W. Articles by Chuang, D.-M.

 Previous Article  |  Next Article 

The Journal of Neuroscience, November 1, 1999, 19(21):9654-9662

Involvement of Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH) and p53 in Neuronal Apoptosis: Evidence That GAPDH Is Upregulated by p53

Ren-Wu Chen¹, Paul A. Saunders¹, Huafeng Wei¹, Zhuangwu Li², Prem Seth², and De-Maw Chuang¹

¹ Section on Molecular Neurobiology, Biological Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, and ² Medical Breast Cancer Section, Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892

We recently reported that cytosine arabinoside (AraC)-induced apoptosis of cerebellar neurons involves the overexpression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH). The present study was undertaken to investigate whether p53 and/or Bax overexpression participates in the AraC-induced apoptosis of cerebellar granule cells and, if so, the relationship between p53 induction and GAPDH overexpression in these cells.

AraC-induced apoptosis of cerebellar granule cells was preceded by an increase in levels of p53 mRNA and protein detected between 1 and 8 hr after treatment. The mRNA level for a p53 target gene, Bax, was also increased. The increase in GAPDH mRNA lasted longer than that of either p53 or Bax, and the level of GAPDH protein in the particulate fraction increased after induction of GAPDH mRNA. The antisense oligonucleotide to p53 protected granule cells from AraC-induced chromatin condensation, internucleosomal cleavage, and apoptotic death. The inhibition of p53 expression by the p53 antisense oligonucleotide not only blocked the expression of Bax but also partially suppressed the increased GAPDH mRNA and protein levels. Conversely, the suppression of GAPDH expression and subsequent attenuation of apoptosis of granule cells by GAPDH antisense oligonucleotide did not influence the expression of p53 or Bax. Cerebellar granule cells prepared from p53 knock-out mice were resistant to AraC toxicity, and the p53 gene knock-out suppressed AraC-upregulated GAPDH expression. Moreover, infection of PC12 cells with an adenoviral vector containing p53 gene dramatically increased GAPDH expression and triggered cell apoptosis. These results suggest that AraC-induced apoptosis of cerebellar granule cells involves the expression of both GAPDH and p53 and that, similar to Bax, GAPDH is upregulated by p53 after exposure to the apoptotic insult.

Key words: p53; GAPDH; cerebellar granule cell; PC12; cytosine arabinoside; apoptosis; adenovirus

---

Copyright © 1999 Society for Neuroscience  0270-6474/99/19219654-09$05.00/0

This article has been cited by other articles:

				P. Piantoni, M. Bionaz, D. E. Graugnard, K. M. Daniels, R. M. Akers, and J. J. Loor Gene Expression Ratio Stability Evaluation in Prepubertal Bovine Mammary Tissue from Calves Fed Different Milk Replacers Reveals Novel Internal Controls for Quantitative Polymerase Chain Reaction J. Nutr., June 1, 2008; 138(6): 1158 - 1164. [Abstract] [Full Text] [PDF]

				J. I. Luoma and L. Zirpel Deafferentation-Induced Activation of NFAT (Nuclear Factor of Activated T-Cells) in Cochlear Nucleus Neurons during a Developmental Critical Period: A Role for NFATc4-Dependent Apoptosis in the CNS J. Neurosci., March 19, 2008; 28(12): 3159 - 3169. [Abstract] [Full Text] [PDF]

				Z.-X. Du, H.-Q. Wang, H.-Y. Zhang, and D.-X. Gao Involvement of Glyceraldehyde-3-Phosphate Dehydrogenase in Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand-Mediated Death of Thyroid Cancer Cells Endocrinology, September 1, 2007; 148(9): 4352 - 4361. [Abstract] [Full Text] [PDF]

				M. Bionaz and J. J. Loor Identification of reference genes for quantitative real-time PCR in the bovine mammary gland during the lactation cycle Physiol Genomics, May 11, 2007; 29(3): 312 - 319. [Abstract] [Full Text] [PDF]

				G. Tezel, X. Yang, and J. Cai Proteomic Identification of Oxidatively Modified Retinal Proteins in a Chronic Pressure-Induced Rat Model of Glaucoma Invest. Ophthalmol. Vis. Sci., September 1, 2005; 46(9): 3177 - 3187. [Abstract] [Full Text] [PDF]

				A. Caricasole, A. Copani, F. Caraci, E. Aronica, A. J. Rozemuller, A. Caruso, M. Storto, G. Gaviraghi, G. C. Terstappen, and F. Nicoletti Induction of Dickkopf-1, a Negative Modulator of the Wnt Pathway, Is Associated with Neuronal Degeneration in Alzheimer's Brain J. Neurosci., June 30, 2004; 24(26): 6021 - 6027. [Abstract] [Full Text] [PDF]

				D. Vaudry, A. Falluel-Morel, S. Leuillet, H. Vaudry, and B. J. Gonzalez Regulators of Cerebellar Granule Cell Development Act Through Specific Signaling Pathways Science, June 6, 2003; 300(5625): 1532 - 1534. [Abstract] [Full Text] [PDF]

				W. G. Tatton, R. M. E. Chalmers-Redman, W. J. H. Ju, M. Mammen, G. W. Carlile, A. W. Pong, and N. A. Tatton Propargylamines Induce Antiapoptotic New Protein Synthesis in Serum- and Nerve Growth Factor (NGF)-Withdrawn, NGF-Differentiated PC-12 Cells J. Pharmacol. Exp. Ther., May 1, 2002; 301(2): 753 - 764. [Abstract] [Full Text] [PDF]

				S. H. Min, R. C. M. Simmen, L. Alhonen, M. Halmekyto, C. W. Porter, J. Janne, and F. A. Simmen Altered Levels of Growth-related and Novel Gene Transcripts in Reproductive and Other Tissues of Female Mice Overexpressing Spermidine/Spermine N1-Acetyltransferase (SSAT) J. Biol. Chem., January 25, 2002; 277(5): 3647 - 3657. [Abstract] [Full Text] [PDF]

				Y. Wang, T. Hayashi, C.-F. Chang, Y.-H. Chiang, L.-I Tsao, T.-P. Su, C. Borlongan, and S.-Z. Lin Methamphetamine Potentiates Ischemia/Reperfusion Insults After Transient Middle Cerebral Artery Ligation Stroke, March 1, 2001; 32(3): 775 - 782. [Abstract] [Full Text] [PDF]

				Z.-H. Qin, Y. Wang, K. K. Kikly, E. Sapp, K. B. Kegel, N. Aronin, and M. DiFiglia Pro-caspase-8 Is Predominantly Localized in Mitochondria and Released into Cytoplasm upon Apoptotic Stimulation J. Biol. Chem., March 9, 2001; 276(11): 8079 - 8086. [Abstract] [Full Text] [PDF]

				A. Lakkaraju, J. M. Dubinsky, W. C. Low, and Y.-E. Rahman Neurons Are Protected from Excitotoxic Death by p53 Antisense Oligonucleotides Delivered in Anionic Liposomes J. Biol. Chem., August 17, 2001; 276(34): 32000 - 32007. [Abstract] [Full Text] [PDF]

				A. J. Barber, M. Nakamura, E. B. Wolpert, C. E. N. Reiter, G. M. Seigel, D. A. Antonetti, and T. W. Gardner Insulin Rescues Retinal Neurons from Apoptosis by a Phosphatidylinositol 3-Kinase/Akt-mediated Mechanism That Reduces the Activation of Caspase-3 J. Biol. Chem., August 24, 2001; 276(35): 32814 - 32821. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help