2004 Fiscal Year Final Research Report Summary
Effect of protein nitration on peri-gingivitis and inflammatory regulation mechanism involving nitration and de-nitration.
| 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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| Keywords | peri-gingivitis / nitric oxide / nitrated protein / inflammation / signal transduction / apotosis (cell death) / cultured cells / neural stem cells |
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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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[Journal Article] RNA interfering approach for clarifying the PPARγ-pathway using lentiviral vector expressing short hairpin RNA.2004
Author(s)
Katayama, K., Wada, K., Miyoshi, H., Ohashi, K., Tachibana, M., Furuki, R., Mizuguchi, H., Hayakawa, T., Nakajima, A., Tsutsumi, Y., Kadowaki, T., Nakagawa, S., Kamisaki, Y., Mayumi, T.
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Journal Title
FEBS Letters 560
Pages: 178-182
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Nonylphenol induces the death of neural stem cells due to activation of the caspase cascade and regulation of the cell cycle.2004
Author(s)
Kudo, C., Wada, K., Masuda, T., Yonemura, T., Shibuya, A., Fujimoto, Y., Nakajima, A., Niwa, H., Kamisaki, Y.
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Journal Title
Journal of Neurochemistry 88
Pages: 1416-1423
Description
「研究成果報告書概要(和文)」より
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[Journal Article] A novel PPARγ-gene therapy to control inflammation associated with inflammatory bowel disease in a murine model.2003
Author(s)
Katayama, K., Wada, K., Nakajima, A., Mizuguchi, H., Hayakawa, T., Nakagawa, S., Kadowaki, T., Nagai, R., Kamisaki, Y., Blumberg, R.S., Mayumi, T.
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Journal Title
Gastroenterology 124
Pages: 1315-1324
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Histone H1,2 is a substrate for denitrase, an activity that reduces nitrotyrosine immunoreactivity in proteins.2003
Author(s)
Irie, Y., Saeki, M., Kamisaki, Y., Martin, E., Murad, F.
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Journal Title
Proc Natl Acad Sci USA 100
Pages: 5634-5639
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Diclofenac inhibits proliferation and differentiation of neural stem cells.2003
Author(s)
Kudo, C., Kori, M., Matsuzaki, K., Yamai, K., Nakajima, A., Shibuya, A., Niwa, H., Kamisaki, Y., Wada, K.
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Journal Title
Biochemical Pharmacology 66
Pages: 289-295
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Histone H1,2 is a substrate for denitrase, an activity that reduces nitrotyrosine immmunoreactivity in proteins.2003
Author(s)
Irie, Y., Saeki, M., Kamisaki, Y., Martin, E., Murad, F.
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Journal Title
Proc Natl Acad Sci USA 100
Pages: 5634-5639
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Nitration of PPARγ inhibits ligand-dependent translocation into the nucleus in a macrophage-like cell line, RAW 264.2002
Author(s)
Shibuya, A., Wada, K., Nakajima, A., Saeki, M., Katayama, K., Mayumi, T., Kadowaki, T., Niwa, H., Kamisaki, Y.
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Journal Title
FEBS Letters 525(1-3)
Pages: 43-47
Description
「研究成果報告書概要(和文)」より
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[Journal Article] PPARγ ligands inhibit nitrotyrosine formation and inflammatory mediator expressions in adjuvant-induced rheumatoid arthritis mice.2002
Author(s)
Shiojiri, T., Wada, K., Nakajima, A., Katayama, K., Shibuya, A., Kudo, C., Kadowaki, T., Mayumi, T., Yura, Y., Kamisaki, Y.
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Journal Title
European Journal of Pharmacology 448
Pages: 231-238
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Strong involvement of nitric oxide derivatives on the pathogenesis of nonalcholoic steatopathies.
Author(s)
Yoneda, M., Wada, K., Fujita, K., Kirikoshi, H., Saitoh, S., Nakane, D., Blumberg, R.S., Kamisaki, Y., Murad, F., Nakajima, A.
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Journal Title
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Strong involvement of nitric oxide derivatives on the pathogenesis of nonalcholoic steatopathies.
Author(s)
Yoneda, M., Wada, K., Fujita, K., Kirikoshi, H., Saitoh, S., Nakane, D., Blumberg, R.S., Kamisaki, Y., Murad, F., Nakajima, A.
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Journal Title
Description
「研究成果報告書概要(欧文)」より
