Discovery of Innovative lipid lowering peptides by targetting the bio-molecule and Creation of novel screening technology

2016 Fiscal Year Final Research Report

• Project/Area Number: 26292067
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Food science
• Research Institution: Gifu University
• Principal Investigator: Nagaoka Satoshi 岐阜大学, 応用生物科学部, 教授 (50202221)
• Co-Investigator(Kenkyū-buntansha): 島田 昌也 岐阜大学, 応用生物科学部, 准教授 (10576755) ; 上野 義仁 岐阜大学, 応用生物科学部, 教授 (20250467) ; 本多 裕之 名古屋大学, 工学研究科, 教授 (70209328)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: コレステロール / ペプチド / ミセル / 胆汁酸 / 動脈硬化 / ラクトスタチン / CYP7A1 / HepG2

Outline of Final Research Achievements

We found that a novel cholesterol lowering milk peptide, lactostatin (IIAEK) activates cholesterol 7α-hydroxylase (CYP7A1) in HepG2 cells. We tried to clarify the molecular basis of the activation of cholesterol degradation by lactostatin in HepG2 cells. Lactostatin significantly and specifically increased CYP7A1 mRNA level in HepG2 cells. The protein level of CYP7A1 and its gene promoter activity determined by luciferase assay were increased by lactostatin. We have identified that the target promoter region of CYP7A1 gene mediated by lactostatin is the HNF3α responsive element. We found that HNF3α knockdown by siRNA inhibited the activation of CYP7A1 protein expression. By using the photo-affinity labelling technieque by diazirine and click chemistry, we can detect the protein having an affinity to lactostatin in vitro. Cholesterol absorption inhibitory peptide, VAWWMY exhibit the increase in micellar particle size by the electorical binding with taurocholate.

Free Research Field

農学