Metabolomic Identification of Novel Regulators of Cardiac Oxidative Stress in Heart Failure
| Project/Area Number |
26461070
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Cardiovascular medicine
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| Research Institution | Kobe University |
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Principal Investigator |
TOH RYUJI 神戸大学, 医学研究科, 特命准教授 (50379418)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 心不全 / メタボローム解析 / βヒドロキシ酪酸 / ケトン体 / 2-アミノ酪酸 / グルタチオン |
|---|
| Outline of Final Research Achievements |
A comprehensive quantification of serum metabolites in patients with atrial septal defect revealed that circulating levels of β-hydroxybutyrate (βOHB) and 2-aminobutyric acid (2-AB) reflected hemodynamic changes. First, we demonstrated that oxidative stress can cause myocardial βOHB accumulation by downregulation of SCOT, a key enzyme of ketone body utilization. Since we found that βOHB has anti-oxidative properties, the accumulation of myocardial βOHB may serve as a compensatory response against oxidative stress. Next, we newly revealed that 2-AB modulates glutathione (GSH) homeostasis. We proved that 2-AB is a byproduct of cysteine in GSH synthetic pathway. Intriguingly, we revealed that 2-AB increased intracellular GSH levels by activating AMPK, and exert protective effects against oxidative stress in cardiomyocytes. Furthermore, oral administration of 2-AB increased both circulating and myocardial GSH levels in mouse model of heart failure.
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Report
(4 results)
Research Products
(11 results)
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[Journal Article] 2-Aminobutyric acid modulates glutathione homeostasis in the myocardium.2016
Author(s)
Irino Y, Toh R, Nagao M, Mori T, Honjo T, Shinohara M, Tsuda S, Nakajima H, Satomi-Kobayashi S, Shinke T, Tanaka H, Ishida T, Miyata O, Hirata KI.
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Journal Title
Sci Rep.
Volume: -
Issue: 1
Pages: 36749-36749
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Presentation] GCMSを用いた心不全バイオマーカー探索2014
Author(s)
Yasuhiro Irino, Ryuji Toh, Takeshige Mori, Manabu Nagao, Tomoyuki Honjo, Seimi Satomi-Kobayashi, Toshiro Shinke, Tatsuro Ishida, Okiko Miyata, and Ken-ichi Hirata
Organizer
第39回日本医用マススペクトル学会年会
Place of Presentation
千葉 日本
Year and Date
2014-10-16 – 2014-10-17
Related Report
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[Presentation] 心不全における新たなバイオマーカーとしての2-Aminobutyric acidの可能性2014
Author(s)
Ryuji Toh, Yasuhiro Irino, Takeshige Mori, Manabu Nagao, Tomoyuki Honjo, Seimi Satomi-Kobayashi, Tatsuro Ishida, Okiko Miyata, and Ken-ichi Hirata
Organizer
第18回 日本心不全学会学術集会
Place of Presentation
大阪 日本
Year and Date
2014-10-10 – 2014-10-12
Related Report
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