| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Research Abstract |
This study aimed to establish a methodology to clarify drug efflux function of P-glycoprotein (P-gp) at the blood-brain barrier (BBB) in disease conditions. We experimentally demonstrated that, in the disease which the absolute protein expression level of P-gp changes (epilepsy), the in vivo function of P-gp at the BBB can be reconstructed from in vitro by integrating the efflux activity per one P-gp molecule measured in its overexpressing cell lines and the absolute expression level in isolated brain capillaries. We found that, in the disease condition which the efflux activity per one P-gp molecule changes (inflammatory oxidative stress), the phosphorylation level of caveolin1 Tyr14 is one of the biomarkers to estimate the change of the activity. We also demonstrated the reconstruction of P-gp function in monkeys as well as rodents, and opened the new way to clarify the efflux function of P-gp at the human BBB in diseases from in vitro system.
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