| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Research Abstract |
Connexin-forming channels regulates cell survival with little information available regarding its mechanisms. Using a ischemic renal injury model, we explored the potential mechanisms of Cx43-forming channels on renal cell survival. Our results showed that Cx43 influenced cell susceptibility to ischemic renal injury. Cells with higher level of Cx43 were more vulnerable to ischemic oxidative injury. On the contrary, cells with no or lower level of Cx43 were resistant. Further analysis revealed that oxidative stimuli activated Cx43 hemichannels, leading to extracellular loss of ATP. The released ATP, in turn, suppressed AMPK activation through purinergistic receptor-mediated activation of AKT and mTOR. Suppression of hemichannels enhanced AMPK activation, thus protecting cells from oxidative injury. Our study indicates that Cx43 hemichannels determines cell susceptibility to oxidative injury. Targeting Cx43 could be developed for prevention and treatment of ischemic renal injury.
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