Roles of lipoprotein receptor mediated signal transduction in metabolic syndrome
| Project/Area Number |
17380081
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Food science
|
|---|
| Research Institution | Ehime University |
|---|
Principal Investigator |
FUJINO Takahiro Ehime University, Integrated Center for Sciences, Associate Professor (40292312)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
MASUDA Seizo Ehime University, Integrated Center for Sciences, Senior Assistant Professor (50363263)
NOSE Masato Ehime University, Graduate School of Medicine, Professor (70030913)
|
|---|
| Project Period (FY) |
2005 – 2007
|
| Project Status |
Completed (Fiscal Year 2007)
|
| Budget Amount *help |
¥15,700,000 (Direct Cost: ¥14,800,000、Indirect Cost: ¥900,000)
Fiscal Year 2007: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2006: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2005: ¥8,600,000 (Direct Cost: ¥8,600,000)
|
|---|
| Keywords | ApoE / Glvcosvlation / Sialic Acid / Lipoprotein receptor / Central Nervus System / NPCI / コレステロール / 中枢神経 / アポリポプロテインE / リソソーム病 / リポタンパク / 脳神経系 |
|---|
| Research Abstract |
ApoE is a major apoprotein of lipoproteins such as VLDL and chiromicron, which is a massive transporter for cholesterol and triglyceride in the circulation. In the CNS apoE secreted by astrocytes also plays important roles in neurite outgrowth, synaptic maintenance and neuronal repair. Although apoE in the CNS is more highly sialylated than plasma apoE, the contribution of O-glycosyl modification with sialic acid residues to the structure and function of apoE is still unknown. To address this, we construct a recombinant adenovirus directing the expression of apoE2, E3, E4 and their mutant forms in order to introduce into glial cells and mcrophages. Expression of apoE and the mutant forms in glial cells and macrophages from apoE-KO mice followed by lectin blot analysis suggested that C-terminal region of apoE contains one major mucin typel O-glycan with sialic acid at Ser290. The interaction of apoE with lipids forms lipoprotein particles, which are subsequently recognized and catabolized by cell-surface lipoprotein receptors. The analysis of knockout mice lacking both of VLDLR and ApoER2 has revealed that VLDLR and ApoER2 function as receptors for reelin, which is involved in the signaling pathway that control neuronal cell positioning. The binding of reelin to the receptors is inhibited by apoE in vitro. To define the function of lipoprotein receptors in lipoprotein metabolism of the CNS, we generated the double KO mice lacking lipoprotein receptors and NPC1, the lack of which is characterized by degeneration of neuronal cells accumulating unesterified cholesterol and sphingolipids in the CNS. An additional defect of NPC1 in VLDLR KO mice led a more severe phenotype in cerebellum development that observed with either alone and other DKO mice, suggesting that defect of NPC1 weakens the function of apoER2 as a reelin receptor.
|
Report
(4 results)
Research Products
(19 results)
-
-
[Journal Article] Deficiency of the very low-density lipoprotein(vldl) receptors in streptozotocin-induced diabetic rats : insulin-dependency of the vidl receptor2005
Author(s)
Iwasaki, T., Takahashi, S., Takahashi, M., Zenimaru, Y., Kujiraoka, T., Ishihara, M., Nagano, M., Suzuki, J., Miyamori, I., Naiki, H., Sakai, J., Fuiino, T., Norman, E., Miller, N. E., Yamamoto, T. T., Hattori, H
-
Journal Title
Endocrinology 146
Pages: 3286-3294
Description
「研究成果報告書概要(欧文)」より
Related Report
-
-
[Presentation] Expression of Fraser syndrome-like phenotype with disruption of GRIP1b and the importance of GRIP1b in functional link with Fras12008
Author(s)
Takahiro, Fuiino, Toyoki, Nishimura, Mingzhe, Liu, Zhong, Wang, Yuki, Tanaka, Masato, Nose
Organizer
Annual Meeting of JSBBA 2008
Place of Presentation
Nagoya
Year and Date
2008-03-27
Description
「研究成果報告書概要(欧文)」より
Related Report
-
-
-
-
[Presentation] Roles of linonrotein receotors in the CNS2008
Author(s)
Zhong, Wang, Seiji, Matsuda, Mingzhe, Liu, Yuki, Tanaka, Takahiro, Fuiino
Organizer
The 62th Annual Meeting of the Japan association of anatomists Tyugoku-Shikoku section
Place of Presentation
Kurasiki
Description
「研究成果報告書概要(欧文)」より
Related Report
-
-
-
-
-
-
-
-
-
-
-
