Gaseous molecules controlling metabolic systems
| Project/Area Number |
21500353
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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 |
Neurochemistry/Neuropharmacology
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| Research Institution | Keio University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
ISHIKAWA Mami 自治医科大学, 医学部, 准教授 (60212859)
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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: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 脳血流代謝カップリング / 一酸化炭素 / 硫化水素 / ガスバイオロジー / heme oxygenase / 脳血流循環代謝 / 低酸素応答 / 質量分析イメージング / neurovascular coupling / cystathionine β-synthase |
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| Research Abstract |
Enhancement of cerebral blood flow by hypoxia is critical for brain function, but signaling systems underlying its regulation have been unclear. We report a novel pathway mediating hypoxia-induced cerebral vasodilation in studies monitoring vascular disposition in cerebellar slices as well as in intact mouse brains employing two-photon intravital laser scanning microscopy. In this cascade, hypoxia elicits cerebral vasodilation via the coordinate actions of hydrogen sulfide(H_2S) formed by cystathionine.-synthase(CBS) and carbon monoxide(CO) generated by heme oxygenase(HO)-2. Hypoxia diminishes CO generation by HO-2, an oxygen(O_2) sensor. The constitutive CO physiologically inhibits CBS, so that hypoxia leads to increased levels of H_2S that mediate the vasodilation of pre-capillary arterioles. Mice with targeted deletion of HO-2 or CBS display impaired vascular responses to hypoxia. Thus, in intact adult brain cerebral cortex of HO-2-null mice, imaging mass spectrometry reveals an impaired ability to maintain ATP levels on hypoxia.
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Report
(4 results)
Research Products
(46 results)
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[Journal Article] Hypoxic regulation of the cerebral microcirculation is mediated by a carbon monoxide-sensitive hydrogen sulfide pathway2012
Author(s)
Morikawa T., Kajimura M., Nakamura T., Hishiki T., Nakanishi T., Yukutake Y., Nagahata Y., Ishikawa M., Hattori K., Takenouchi T., Takahashi T., Ishii I., Matsubara K., Kabe Y., Uchiyama S., Nagata E., Gadalla M.M., Snyder S.H., Suematsu M.
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Journal Title
Proc Natl Acad Sci USA
Volume: 109
Issue: 4
Pages: 1293-1298
DOI
Related Report
Peer Reviewed
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[Journal Article] Hypoxia-sensitive fluorescent probes for in vivo real-time fluorescence imaging of acute ischemia.2010
Author(s)
Kiyose K, Hanaoka K, Oushiki D, Nakamura T, Kajimura M, Suematsu M, Nishimatsu H, Yamane T, Terai T, Urano Y, Hirata Y, Nagano T.
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Journal Title
Journal of the American Chemical Society
Volume: 132
Pages: 15846-15848
Related Report
Peer Reviewed
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[Presentation] CO-H_2S cascade controls brain microvascular tone during hypoxia2011
Author(s)
Kajimura M., Morikawa T., Nakamura T., Hattori K., Hishiki T., Nagahata Y., and Suematsu M
Organizer
Joint meeting of the European Society for Microcirculation and the German Society of Microcirculation and Vascular Biology
Place of Presentation
Ludwig-Maximilians-University, Munich Germany
Year and Date
2011-10-15
Related Report
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[Presentation] CO-H_2S cascade controls brain microvascular tone during hypoxia2011
Author(s)
Kajimura M., Morikawa T., Nakamura T., Hattori K., Hishiki T., Nagahata Y., Suematsu M.
Organizer
Joint meeting of the European Society for Microcirculation and the German Society of Microcirculation and Vascular Biology
Place of Presentation
Ludwig-Maximilians-University, Munich Germany(招待講演)
Year and Date
2011-10-15
Related Report
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[Presentation] Paradoxical ATP elevation in ischemic penumbra revealed by quantitative imaging mass spectrometry2010
Author(s)
Hattori K, Kajimura M, Hishiki T, Nakanishi T, Kubo A, Nagahata Y, Yachie-Kinoshita A, Matsuura T, Setou M, Suematsu M.
Organizer
The 40^<th> Annual Meeting for Neuroscience
Place of Presentation
San Diego, USA.
Year and Date
2010-11-15
Related Report
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