|Budget Amount *help
¥45,110,000 (Direct Cost: ¥34,700,000、Indirect Cost: ¥10,410,000)
Fiscal Year 2015: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2014: ¥13,390,000 (Direct Cost: ¥10,300,000、Indirect Cost: ¥3,090,000)
Fiscal Year 2013: ¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2012: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
|Outline of Final Research Achievements
The purpose of the present research was to clarify the molecular mechanisms of the functional plasticity of the blood-brain barrier (BBB) transport system as a dynamic interface. By quantitative targeted absolute proteomics and in vivo study, the changes in the expression levels of transporter proteins and the P-glycoprotein transport function at the BBB were clarified in mouse models of epilepsy and inflammation. Quantitative phospho-proteomics and in vitro study revealed the change in P-glycoprotein transport and its regulatory mechanisms via the phosphorylation of the assembly protein and/or second messenger protein under the exposures of oxidative stress and inflammatory cytokines in human brain capillary endothelial cells. Therefore, the functional plasticity of the BBB transport system would be produced by not only the changes in the expression levels of transporter proteins on the plasma membrane but also the phosphorylation of the signal transduction-related proteins.