DNA polymerase-beta is required for 1-methyl-4-phenylpyridinium-induced apoptotic death in neurons

Apoptosis : an International Journal on Programmed Cell Death
Zhentao ZhangTao Wang

Abstract

The biochemical pathways that mediate the degeneration of dopaminergic neurons in the substantia nigra of patients with Parkinson's disease are largely unknown. Recently, aberrant cell cycle events have been shown to be associated with neuronal death in several neurodegenerative diseases. In the present study, we investigated the role of DNA polymerases (DNA pols) in 1-methyl-4-phenylpyridinium (MPP(+))-induced neuronal apoptosis in cerebellar granule cells. After exposure to MPP(+), the neurons entered S phase of the cell cycle. Neuronal cell cycle re-entry and apoptosis were attenuated by flavopiridol, which is a broad inhibitor of cyclin-dependent kinases (CDKs). MPP(+) exposure significantly increased the expression of DNA pol-beta and primase but did not affect the expression of the canonical replicative DNA pols, including DNA pol-delta and pol-epsilon. Dideoxycytidine, which is a pharmacological inhibitor of DNA pol-beta, attenuated the neuronal apoptosis mediated by MPP(+). In a similar manner, the expression of a dominant negative form of DNA pol-beta was also neuroprotective. These results suggest that DNA pol-beta may have a causal role in MPP(+)-induced neuronal apoptosis.

References

Oct 23, 1997·Proceedings of the National Academy of Sciences of the United States of America·Y DuS M Paul
Feb 6, 2002·Journal of Molecular Biology·Laurence ServantJean-Sébastien Hoffmann
Jun 1, 2002·Science·Errol C FriedbergMiroslav Radman
Sep 19, 2002·Trends in Pharmacological Sciences·Marie KnockaertLaurent Meijer
Oct 24, 2002·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·N S RajiKalluri Subba Rao
Oct 25, 2002·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Agata CopaniFerdinando Nicoletti
Jan 17, 2003·Journal of Neuropathology and Experimental Neurology·Kelly L Jordan-SciuttoCristian L Achim
Feb 25, 2003·The American Journal of Pathology·Srikanth Ranganathan, Robert Bowser
Apr 23, 2003·The Journal of Cell Biology·Yoshiki ArakawaShuh Narumiya
Sep 16, 2003·Neuron·William Dauer, Serge Przedborski
Dec 3, 2003·Cell Death and Differentiation·L A GreeneD X Liu
Mar 25, 2004·Lancet Neurology·Xiongwei ZhuMark A Smith
Oct 22, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Karl HerrupAgata Copani
Jan 19, 2005·Molecular Neurobiology·Rosa A González-PoloJosé M Fuentes
Jun 1, 2005·Proceedings of the National Academy of Sciences of the United States of America·Simone Di GiovanniAlan I Faden
Jul 19, 2005·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·Sari NeijenhuisConchita Vens
Oct 27, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Agata CopaniFerdinando Nicoletti
Dec 13, 2006·Biochimica Et Biophysica Acta·Yan Yang, Karl Herrup
Feb 9, 2007·Proceedings of the National Academy of Sciences of the United States of America·Yafell SerulleRodolfo R Llinás
Mar 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Günter U HöglingerStéphane Hunot
Jun 29, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Birgit MoschThomas Arendt
Dec 21, 2007·Lancet Neurology·Anthony H V Schapira
Apr 24, 2008·Journal of Neuropathology and Experimental Neurology·Lee J Martin
Sep 20, 2008·Journal of Neurology·Jörg B Schulz
Oct 7, 2008·The Journal of Biological Chemistry·Peter M J Burgers

❮ Previous
Next ❯

Citations

Mar 19, 2013·Behavioral and Brain Functions : BBF·Nian XiongTao Wang
Dec 4, 2012·International Journal of Molecular Sciences·Matthias BosshardBarbara van Loon
Jan 13, 2015·Molecular Neurobiology·Jing XiongTao Wang
Aug 31, 2011·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Aurelio Vazquez de la TorreAntoni Camins
Jun 21, 2011·Neurochemistry International·Aurelio Vazquez de la TorreEster Verdaguer
Sep 3, 2016·Genes·Elisa MentegariEmmanuele Crespan
Jun 21, 2017·Neurochemical Research·Jianyi NiuZhaohui Zhang
Jun 29, 2021·Neurochemistry International·Nishtha MalhotraPravir Kumar

❮ Previous
Next ❯

Related Concepts

Related Feeds

Basal Ganglia

Basal Ganglia are a group of subcortical nuclei in the brain associated with control of voluntary motor movements, procedural and habit learning, emotion, and cognition. Here is the latest research.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Cell Cycle Pathways

Cell cycle is a complex process regulated by several signal transduction pathways and enzymes. Here is the latest research on regulation of cell cycle and cell cycle pathways.

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.