| Project/Area Number |
21591000
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Kumamoto University |
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Principal Investigator |
OKAMOTO Tatsuya 熊本大学, 大学院・生命科学研究部, 助教 (30419634)
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| Co-Investigator(Kenkyū-buntansha) |
FUJII Shigemoto 熊本大学, 大学院・生命科学研究部, 助教 (00325333)
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| Co-Investigator(Renkei-kenkyūsha) |
AKAIKE Takaaki 熊本大学, 大学院・生命科学研究部, 教授 (20231798)
ITOH Takaaki 熊本大学, 大学院・生命科学研究部, 教授 (70168392)
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| Project Period (FY) |
2009 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | ウイルス性肺炎 / 急性呼吸窮迫症候群 / 酸化ストレス応答 / インフルエンザ / 3-ニトロチロシン / 8-ニトロ-cGMP / S-グアニル化 / 治療戦略 / 8-ニトロcGMP / 8-ニトロチロシン / プロテオミクス解析 |
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| Research Abstract |
Nitric oxide(NO) and reactive oxygen species(ROS) have been suggested to be involved in the pathogenesis of ARDS. NO/ROS have also been reported to induce nitration of tyrosine and guanine leading to the formation of 3-nitrotyrosine(3-NT) and 8-nitro-cGMP, respectively. In this study, we found significant increase of 3-NT and 8-nitro-cGMP levels in the lungs of influenza virus(IFV)-infected mice. Strong induction of an antioxidant enzyme heme oxygenase-1 was also detected in the lung of infected mice. Upregulation of HO-1 in parallel with the formation of 8-nitro-cGMP suggested that formation of 8-nitro-cGMP or 3-NT may be involved in the oxidative stress responses in the IFV-infected mice. Therefore, we postulated that formation of 3-NT might also influence on the disease activity of ARDS in humans. We performed a case-control study for plasma 3-NT levels of ARDS patients with/without IFV infection and of control subjects. The ARDS patients with IFV infection had significantly higher 3-NT levels than the control subjects. Additionally, ARDS patients with high 3-NT levels had better survival rate compared to patients with low 3-NT levels. These data thus suggest that NO/ROS-mediated formation of 3-NT or 8-nitro-cGMP may be involved in a unique signal transduction contributing to the host defense or tissue repair against IFV-induced fulminant pneumonia/ARDS.
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