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

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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-β and primase but did not affect the expression of the canonical replicative DNA pols, including DNA pol-δ and pol-ε. Dideoxycytidine, which is a pharmacological inhibitor of DNA pol-β, attenuated the neuronal apoptosis mediated by MPP+. In a similar manner, the expression of a dominant negative form of DNA pol-β was also neuroprotective. These results suggest that DNA pol-β may have a causal role in MPP+-induced neuronal apoptosis.

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Acknowledgment

This work was supported by grants from the Program of National Natural Science Foundation of China (No. 30570627 and No. 30870866).

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Authors and Affiliations

  1. Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, People’s Republic of China

    Zhentao Zhang, Xuebing Cao, Nian **ong, Hongcai Wang, **sha Huang, Shenggang Sun, Zhihou Liang & Tao Wang

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  1. Zhentao Zhang
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  2. Xuebing Cao
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  8. Tao Wang
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Correspondence to Tao Wang.

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The authors Zhentao Zhang and Xuebing Cao are equally contributed to this work.

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Zhang, Z., Cao, X., **ong, N. et al. DNA polymerase-β is required for 1-methyl-4-phenylpyridinium-induced apoptotic death in neurons. Apoptosis 15, 105–115 (2010). https://doi.org/10.1007/s10495-009-0425-8

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