Regulation of inflammation responses by HDL formation

• Project/Area Number: 25850070
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Applied biochemistry
• Research Institution: Kyoto University (2014); The University of Tokushima (2013)
• Principal Investigator: NAGAO Kohjiro 京都大学, 工学(系)研究科(研究院), 助教 (40587325)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: コレステロール / ABCA1 / HDL

Outline of Final Research Achievements

ABCA1 mediates the efflux of cholesterol and phospholipids into apoA-I to form HDL, which is important in not only the prevention of atherosclerosis but also the regulation of inflammation responses. To develop a novel method for the evaluation of HDL formation, we prepared an apoA-I-POLARIC by labeling the apoA-I variant with a hydrophobicity-sensitive fluorescence probe that detects the environmental change around apoA-I during HDL formation. THP-1 macrophage-mediated HDL formation could be measured using apoA-I-POLARIC. These results demonstrate that HDL formation by ABCA1-expressing cells can be specifically detected by sensing hydrophobicity change in apoA-I, thus providing a novel method for assessing HDL formation.

Research Products

• [Journal Article] Direct detection of ABCA1-dependent HDL formation based on lipidation-induced hydrophobicity change in apoA-I. (2014)
  • Author(s): Risa Omura, Kohjiro Nagao, Norihiro Kobayashi, Kazumitsu Ueda, and Hiroyuki Saito
  • Journal Title: J Lipid Res. Volume: 55 Issue: 11 Pages: 2423-2431
  • DOI: 10.1194/jlr.d049445
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The roles of C-terminal helices of human apolipoprotein A-I in formation of high-density lipoprotein particles. (2014)
  • Author(s): Nagao, K., Hata, M., Tanaka, K., Takechi, Y., Nguyen, D., Dhanasekaran, P., Lund-Katz, S., Phillips, M. C., and Saito, H.
  • Journal Title: Biochim. Biophys. Acta-Mol. Cell Biol. Lipids Volume: 1841 Issue: 1 Pages: 80-87
  • DOI: 10.1016/j.bbalip.2013.10.005
  • Peer Reviewed
• [Journal Article] Interaction of Thioflavin T with Amyloid Fibrils of Apolipoprotein A-I N-terminal Fragment: Resonance Energy Transfer Study. (2014)
  • Author(s): Girych, M., Gorbenko, G., Trusova, V., Adachi, E., Mizuguchi, C., Nagao, K., Kawashima, H., Akaji, K., Lund-Katz, S., Phillips, M. C., and Saito, H.
  • Journal Title: J. Struct. Biol. Volume: 185 Issue: 1 Pages: 116-124
  • DOI: 10.1016/j.jsb.2013.10.017
  • Peer Reviewed
• [Journal Article] The Extreme N-terminal Region of Human Apolipoprotein A-I Has a Strong Propensity to Form Amyloid Fibrils (2014)
  • Author(s): Adachi, E., Kosaka, A., Tsuji, K., Mizuguchi, C., Kawashima, H., Shigenaga, A., Nagao, K., Akaji, K., Otaka, A., and Saito, H.
  • Journal Title: FEBS Lett. Volume: 588 Issue: 3 Pages: 389-394
  • DOI: 10.1016/j.febslet.2013.11.031
  • Peer Reviewed
• [Journal Article] ATPase activity of nucleotide binding domains of human MDR3 in the context of MDR1 (2013)
  • Author(s): Ishigami, M.. Tominaga, Y., Nagao, K., Kimura, Y., Matsuo, M., Kioka, N. and Ueda, K
  • Journal Title: Biochim Biophys Acta-MCBL Volume: 1831 Issue: 4 Pages: 683-690
  • DOI: 10.1016/j.bbalip.2012.12.016
  • Peer Reviewed
• [Journal Article] 24(S)-hydroxycholesterol is actively eliminated from neuronal cells by ABCA1. (2013)
  • Author(s): Matsuda, A., Nagao, K, Matsuo, M., Kioka N. and Ueda, K.
  • Journal Title: J. Neurochem. Volume: (in press) Issue: 1 Pages: 93-101
  • DOI: 10.1111/jnc.12275
  • Peer Reviewed
• [Presentation] Apolipoprotein A-I周囲環境変化に着目した新規HDL形成測定法の開発 (2014)
  • Author(s): 長尾耕治郎, 大村理紗, 斎藤博幸
  • Organizer: 日本農芸化学会2014年度大会
  • Place of Presentation: 明治大学（神奈川県）
• [Presentation] HDL形成におけるapolipoprotein A-IのC末領域の機能 (2013)
  • Author(s): 長尾耕治郎, 端茉美, 田中健斗, 川上徹, 相本三郎, 斎藤博幸
  • Organizer: 膜シンポジウム2013
  • Place of Presentation: 京都府立医科大学（京都府）