2011 Fiscal Year Final Research Report
Involvement of oxidative stress in the pathogenesis of ARDS associated with viral pneumonia
| 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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| 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 |
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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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Research Products
(50 results)
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[Journal Article] Vascular responses to 8-nitro-cyclic GMP in non-diabetic and diabetic mice2011
Author(s)
Yoshiko Tokutomi, Keiichiro Kataoka, Eiichiro Yamamoto, Taishi Nakamura, Masaya Fukuda, Hisato Nako, Kensuke Toyama, Yi-Fei Dong, Ahmed Khandaker Ahtesham, Tomohiro Sawa, Takaaki Akaike and Shokei Kim-Mitsuyama
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Journal Title
Br J Pharmacol
Volume: 162
Pages: 1884-1893
DOI
Peer Reviewed
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[Journal Article] The critical role of nitric oxide signaling, via protein S-guanylation and nitrated cyclic GMP, in the antioxidant adaptive response2010
Author(s)
Shigemoto Fujii, Tomohiro Sawa, Hideshi Ihara, Kit I. Tong, Tomoaki Ida, Tatsuya Okamoto, Ahmed Khandaker Ahtesham, Yu Ishima, Hozumi Motohashi, Masayuki Yamamoto, and Takaaki Akaike
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Journal Title
J Biol Chem
Volume: 285
Pages: 23970-23984
Peer Reviewed
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[Presentation] Helicobacter cinaedi infection as a potential etiological factor in atrial arrhythmia and atherosclerosis2011
Author(s)
Tatsuya Okamoto, Shahzada Khan, Koji Enomoto, Naomi Sakashita, Kohta Oyama, Shigemoto Fujii, Tomohiro Sawa, Motohiro Takeya, Hisao Ogawa, Kunihiko Matsui, Hiroshige Yamabe, Takaaki Akaike
Organizer
International Union of Microbiological Societies 2011 Congress
Place of Presentation
Sapporo Convention Center(Sapporo, Japan)
Year and Date
2011-09-06
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