New concept for treatment of iscgemia/reperfusion injuries brought by metabolomics
| Project/Area Number |
23310136
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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 |
Genome biology
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| Research Institution | Keio University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
KUBO Akiko 慶應義塾大学, 医学部, 特任講師 (50455573)
YACHIE Ayako 慶應義塾大学, 医学部, 共同研究員 (10453549)
HISHIKI Takako 慶應義塾大学, 医学部, 講師 (10338022)
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| Project Period (FY) |
2011-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥15,080,000 (Direct Cost: ¥11,600,000、Indirect Cost: ¥3,480,000)
Fiscal Year 2014: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2013: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2012: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2011: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
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| Keywords | hypoxia / metabolomics / HIF / PHD / iscemia / 低酸素 / 代謝 / 虚血再灌流傷害 / メタボローム / 低酸素応答 / 虚血再灌流 / メタボローム解析 / 心筋梗塞 |
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| Outline of Final Research Achievements |
Cells turn on hypoxic response under the environment where the available oxygen molecules are limited. Hypoxic response is mainly regulated by transcriptional factor HIF (hypoxia-inducible factor), which is also negatively regulated by “oxygen sensor” prolyl-hydroxylase PHDs. Among all PHDs, inactivation of PHD2 alone is sufficient to activate HIF pathway.
Given that hypoxic response is designed for tissue protection under the hypoxic environment such as ischemic diseases, activation of HIF by PHD2-blocade should have beneficial role in ischemia/reperfusion model. Here we reported that inactivation of Phd2 in mice myocardial infarction model revealed smaller infarction size and better cardiac function by maintaining higher ATP with lower oxygen consumption. Our study shed light on new treatment for ischemia reperfusion injuries by targeting oxygen sensor PHD2.
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Report
(5 results)
Research Products
(29 results)
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[Journal Article] Energy management by enhanced glycolysis in G1-phase in human colon cancer cells in vitro and in vivo.2013
Author(s)
Bao Y, Mukai K, Hishiki T, Kubo A, Ohmura M, Sugiura Y, Matsuura T, Nagahata Y, Hayakawa N, Yamamoto T, Fukuda R, Saya H, Suematsu M, Minamishima YA.
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Journal Title
Mol Cancer Res.
Volume: 11
Issue: 9
Pages: 973-985
DOI
Related Report
Peer Reviewed
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[Journal Article] Loss of the retinoblastoma binding protein 2 (RBP2) histone demethylase suppresses tumorigenesis in mice lacking Rb1 or Men12011
Author(s)
Lin W, Cao J, Liu J, Beshiri ML, Fujiwara Y, Francis J, Cherniack AD, Geisen C, Blair LP, Zou MR, Shen X, Kawamori D, Liu Z, Grisanzio C, Watanabe H, Minamishima YA, et al
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Journal Title
Proc Natl Acad Sci U S A
Volume: 108
Issue: 33
Pages: 13379-86
DOI
Related Report
Peer Reviewed
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[Presentation] Energy management by enhanced glycolysis in G1 phase in human colon cancer cells in vivo and in vitro2014
Author(s)
Yan Bao, Kuniaki Mukai, Takako Hishiki, Akiko Kubo, Mitsuyo Ohmura, Yuki Sugiura, Tomomi Matsuura, Yoshiko Nagahata, Noriyo Hayakawa, Takehiro Yamamoto, Ryo Fukuda, Hideyuki Saya, Makoto Suematsu and Yoji Andrew Minamishima
Organizer
Keystone Symposia "Tumor Metabolism (X6)"
Place of Presentation
Whistler, BC, Canada
Related Report
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[Book] 血管医学2012
Author(s)
南嶋 洋司
Total Pages
7
Publisher
メディカルビュー社
Related Report
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[Book] 腎臓2012
Author(s)
南嶋 洋司
Total Pages
5
Publisher
日本腎臓財団
Related Report
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