| Project/Area Number |
25660103
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Food science
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| Research Institution | Nagoya University |
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Principal Investigator |
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 核酸 / 炎症 / 付加体 / ミトコンドリア / マクロファージ / 受容体 / DNA付加体 |
|---|
| Outline of Final Research Achievements |
First, we comprehensively analyzed deoxyguanosine adducts with lipid peroxidation products by LC-MS/MS and detected over 100 adducts. Among them, we identified a novel 2-octenal-dG adduct. We also examined the effects of various nucleotides and nucleosides on the inflammatory responses in J774.1 macrophages, and demonstrated the P2X7-mediated inflammatory signaling of ATP. In addition, we found that some dietary polyphenols inhibited the ATP-derived signaling. Furthermore, we found that the inhibition of proteasome and/or autophagy pathways leads to the extracellular secretion of high-molecular weight nucleic acids (DNA and RNA). In addition, we examined the molecular mechanism for the inflammatory responses upon mitochondrial respiratory inhibition. These results suggested that various nucleic acids, including low- and high-molecular weight nucleic acid derivatives, could induce inflammatory responses in macrophages.
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