| Budget Amount *help |
¥16,510,000 (Direct Cost: ¥12,700,000、Indirect Cost: ¥3,810,000)
Fiscal Year 2016: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2015: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2014: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
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| 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.
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