| Project/Area Number |
14370592
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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 |
Functional basic dentistry
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| Research Institution | Osaka University |
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Principal Investigator |
KAMISAKI Yoshinori Osaka University, Graduate School of Dentistry, Professor, 大学院・歯学研究科, 教授 (40116017)
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| Co-Investigator(Kenkyū-buntansha) |
YONEHARA Norifumi Graduate School of Dentistry, Graduate School of Dentistry, Associate Professor, 大学院・歯学研究科, 助教授 (70124534)
WADA Koichiro Graduate School of Dentistry, Graduate School of Dentistry, Assistant Professor, 大学院・歯学研究科, 講師 (90263467)
SAEKI Makio Graduate School of Dentistry, Graduate School of Dentistry, Instructor, 大学院・歯学研究科, 助手 (30273692)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥13,800,000 (Direct Cost: ¥13,800,000)
Fiscal Year 2004: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2003: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥6,600,000 (Direct Cost: ¥6,600,000)
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| Keywords | peri-gingivitis / nitric oxide / nitrated protein / inflammation / signal transduction / apotosis (cell death) / cultured cells / neural stem cells / 歯肉炎 / PPARγ / 核移行型受容体 / 転写制御因子 |
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| Research Abstract |
In order to clarify the involvement of protein nitration in inflammation, we stimulated cultured cell lines from macrophages (RAW267) by lipopolysaccharide, tumor necrosis factor and peroxynitrite and found that peroxisome proliferator-activated receptor γ(PPARγ), one of steroid hormone receptor superfamily is strongly nitrated. Moreover, the nitrated receptors fail to move into nucleus as a transcription factor in the ligand-dependent mechanism. In addition, this receptor is nitrated in various tissues of animal models during inflammatory condition such as adjuvant-induced arthritis and ischemia-reperfusion induced intestinitis, and even in human liver from hepatitis.
On the other hand, nitrated proteins during inflammation are related to cell death (apoptosis). We found that vanadate inhibits peroxynitrite-induced cell death of SH-SY5Y, that the treatment of neural stem cells with diclofenac, one of anti-inflammatory agents, results in apoptosis by inhibition of cell growth and differentiation, and that caspase-3, which works at the final stage of apoptosis, is regulated by newly found calcium binding proteins. These data indicate the existence of interaction between phosphorylation and nitration systems.
We also searched the mechanism to restore the impaired function of protein by de-nitration and revealed that there is an presumably enzymatic disappearance of nitrated proteins, although it may be one of peptidases which catalyze the specific sequence of nitrated amino acids.
Therefore, although we could not obtain human samples of gingivitis due to the restriction, the nitration is clarified to be involved in the regulatory system during inflammation and may be a possible target of drugs to regulate inflammation.
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