| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
|---|
| Outline of Final Research Achievements |
Mitochondrial ATP-sensitive K+ (mKATP) channels and SAFE (Survivor activating factor enhancement, JAK/STAT) pathway have been proposed to play a key role in cardioprotection.
To explore possible mechanistic links between mKATP channel and SAFE pathway, we measured infarct size after ischemia/reperfusion in rabbit hearts and mitochondrial flavoprotein (FP) fluorescence in rabbit ventricular myocytes using IL6 (JAK activator). Treatment with IL6 after lethal ischemia significantly reduced the infarct size. This infarct size-limiting effect was abolished by the mKATP channel blocker 5-hydroxydecanoate (5HD) or STAT3 inhibitor STATTIC. IL6 augmented the mKATP channel opener-induced FP oxidation. This effect of IL6 was prevented by STATTIC or 5HD.
These results indicate that IL6 potentiates the opening of mKATP channels in a STAT3-dependent manner and further suggest that infarct size-limiting effect of IL6 is mediated, at least in part, by activation of mKATP channels.
|
