| Project/Area Number |
15087207
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Science and Engineering
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| Research Institution | Kumamoto University |
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Principal Investigator |
AKAIKE Takaaki Kumamoto University, Department of Microbiology, Graduate School of Medical Sciences, Professor, 大学院医学学研究部, 教授 (20231798)
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| Co-Investigator(Kenkyū-buntansha) |
SAWA Tomohiro Kumamoto University, Department of Microbiology, Graduate School of Medical Sciences, Research associate, 大学院医学薬学研究部, 助手 (30284756)
芥 照夫 熊本大学, 大学院医学薬学研究部, 助手 (00346975)
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| Project Period (FY) |
2003 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥28,800,000 (Direct Cost: ¥28,800,000)
Fiscal Year 2006: ¥7,200,000 (Direct Cost: ¥7,200,000)
Fiscal Year 2005: ¥7,200,000 (Direct Cost: ¥7,200,000)
Fiscal Year 2004: ¥7,200,000 (Direct Cost: ¥7,200,000)
Fiscal Year 2003: ¥7,200,000 (Direct Cost: ¥7,200,000)
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| Keywords | NO / redox signal / signal transduction / adaptive response / radical / cell death / 8-nitroguanosine / 8-ニトロ-cGMP / 核酸ニトロ化 / ヘムオキシゲナーゼー1 / 核酸にニトロ化 / ヘムオキシゲナーゼ-1 / Nitronyl nitroxide / NOセンサー / NO消去剤 / NO分子機能制御 / PTIO / 細胞シグナル / 細胞保護作用 |
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| Research Abstract |
Nitric oxide (NO) has been suggested to be involved in the pathogenesis of various diseases, including infections, inflammatory diseases, and cancer. We have demonstrated the occurrence of nitratively modified nucleic acids (e.g., 8-nitroguanosine and 8-nitroguanine) in precancerous and cancer tissues, including idiopathic pulmonary fibrosis and human lung cancer, and in urine of smokers. In this study, we identified the formation of novel nitrated cyclic nucleotide, 8-nitroguano sine-3', 5'-cyclic monophosphate (8-nitro-c GMP), in macrophages stimulated with inflammatory cytokine. 8-Nitro-cGMP possesses cGMP-dependent protein kinase-activating potential and unique signal functions independent of cGMP activity. Of great importance is a novel post-translational modification (8-thioalkoxy-cGMP adduct formation) of proteins induced by 8-nitro-cGMP, coined S-guanylation. For example, a redox-sensor signal protein Keap 1 appears to be regulated by 8-nitro-cGMP, via S-guanylation of highly nucleophilic Cys sulfhydrils of Keap 1, leading to the induction of stress adaptive response signals. This study revealed 8-nitro-cGMP to be asecond messenger of NO and shed light on new areas of pathophysiology and chemical biology of signal transduction by NO and cGMP.
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