2007 Fiscal Year Final Research Report Summary
Roles of the defense mechanisms against oxidative damage in nucleic acids for maintenance of brain cells
| Project/Area Number |
18300124
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Kyushu University |
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Principal Investigator |
NAKABEPPU Yusaku Kyushu University, Medical Institute of Bioregulation, Professor (30180350)
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| Project Period (FY) |
2006 – 2007
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| Keywords | Reactive oxygen species / 8-oxoguanine / MTH1 / OGG1 / MUTYH / dopamine neuron / striatal medium spiny neuron / hippocampal neurogenesis |
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| Research Abstract |
The head investigator, Dr. Nakabeppu had shown that oxidation or deamination of bases or nucleotides by reactive oxygen species causes cellular dysfunction through accumulation of such aberrant bases or nucleotides within cells. In this project, we explored molecular pathways causing neuronal cell death or neuronal dysfunction under oxidative stress, by examining Mth1-, Ogg1-, Mutyh,- and Itpa -null mice and cell lines derived from these mutant mice, in comparison to wild-type mice and cell lines. Furthermore, functional analyses of fosB gene coding subunits of AP-1 transcription factor and its downstream target, galectin-1 were performed, in order to explore the regulatory mechanisms for the neurogenesis in hippocampal dentate gyrus under oxidative stress, as well as for the response to oxidative stress in brain. We have achieved the following results for 2 years.
[1] We have demonstrated that oxidation of nucleic acids is one of causes for the neuronal dysfunction of dopamine neurons, using a model mice for Parkinsonism.
[2] We showed that oxidative damage in nucleic acids plays a major role for degeneration of medium spiny neurons in the striatum caused by mitochondrial toxin, 3-nitropropionic acid.
[3] We elucidated the molecular pathways for cell death caused by accumulation of oxidized bases in either nuclear or mitochondrial genomes.
[4] We elucidated the molecular pathway for cell death caused by oxidation of mitochondrial nucleotide pool and the defense mechanism against it.
[5] We explored the sanitizing mechanism for deaminated purine nucleoside triphosphates generated by oxidative deamination.
[6] We have shown that fosB gene is involved in the regulation of neurogenesis in the hippocampal dentate gyrus under oxidative stress.
[7] We demonstrated that galectin-1 promotes neurogenesis in the hippocampal dentate gyrus.
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Research Products
(173 results)
