| 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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| 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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