Clarification of molecular mechanisms of the blood-brain barrier plasticity based on quantitative targeted absolute proteomics

2015 Fiscal Year Final Research Report

• Project/Area Number: 24249011
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Tohoku University
• Principal Investigator: Terasaki Tetsuya 東北大学, 薬学研究科(研究院), 教授 (60155463)
• Co-Investigator(Kenkyū-buntansha): TACHIKAWA Masanori 東北大学, 大学院薬学研究科, 准教授 (00401810) ; NAKADA Mitsutoshi 金沢大学, 医学系, 教授 (20334774) ; WATANABE Michitoshi 東北大学, 大学院薬学研究科, 助教 (40303127) ; HAMADA Junichiro 金沢大学, 医学系, 教授 (40253752) ; UCHIDA Yasuo 東北大学, 大学院薬学研究科, 助教 (70583590)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Keywords: 血液脳関門 / トランスポーター / リン酸化 / 定量プロテオミクス / P-糖蛋白 / 可塑性 / 病態

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.

Free Research Field

薬物動態学、定量プロテオミクス