Comprehensive analysis of the mechanism of novel bioactive lipids transport system.
| Project/Area Number |
21200071
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research on Innovative Areas (Research a proposed research project)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Biological pharmacy
Functional biochemistry
|
|---|
| Research Institution | Osaka University |
|---|
Principal Investigator |
NISHI Tsuyoshi 大阪大学, 産業科学研究所, 准教授 (60403002)
|
|---|
| Co-Investigator(Renkei-kenkyūsha) |
NAKASHIMA Ryosuke 大阪大学, 産業科学研究所, 助教 (20379100)
|
|---|
| Project Period (FY) |
2009 – 2011
|
| Project Status |
Completed (Fiscal Year 2011)
|
| Budget Amount *help |
¥28,730,000 (Direct Cost: ¥22,100,000、Indirect Cost: ¥6,630,000)
Fiscal Year 2011: ¥9,490,000 (Direct Cost: ¥7,300,000、Indirect Cost: ¥2,190,000)
Fiscal Year 2010: ¥9,490,000 (Direct Cost: ¥7,300,000、Indirect Cost: ¥2,190,000)
Fiscal Year 2009: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
|
|---|
| Keywords | 輸送体 / 脂質メディエーター / スフィンゴシン1リン酸 / ABC トランスポーター / 免疫抑制剤 / リンパ球 / 細胞遊走 / 動脈硬化 / オーファン輸送体 / 血管内皮細胞 / MFS型 / 赤血球 / FTY720 / ABCトランスポーター / スフィンゴ脂質 / コレステロール / トランスポーター / 構造機能相関 / ABC輸送体 |
|---|
| Research Abstract |
Sphingosine 1-phosphate (S1P) is one of the most important lipid mediators and essential for cell migration. To elucidate a physiological role of SPNS2 in mammals, we analyzed Spns2-defecient mice. Spns2 transcripts were detected in vascular endothelial cells and S1P secretion were abolished in the vascular endothelial cells prepared from SPNS2-defecient mice. Consequently, blood plasma S1P concentration of SPNS2-defecient mice was reduced to approximately 60% of wild-type. Although about a half of S1P remaining in blood plasma, the blood of SPNS2-deficient mice contained significantly fewer lymphocytes. However, lymphocytes in SPNS2-defecient mice thymus express more S1p1 and show a high migration activity at a lower S1P concentration. These results suggested that S1P at microenvironments around the thymus endothelial cells is rather important for the lymphocytes egress from the thymus than overall S1P concentration in plasma.
Among the constructed various ABC transporters knockout mice, ABCA5 deficinet macrophage decrease cholesterol efflux and enhance the atheroscrelosis. These results suggested various orphan transporters play physiological important lipids odulators.
|
Report
(4 results)
Research Products
(69 results)
-
-
-
-
-
-
-
[Journal Article] The sphingosine 1-phosphate transporter, Spns2 function as an exporter for the phosphorilated form of immunomodulating agent FTY720 from the cells.2011
Author(s)
Hisano, Y., Kobayashi, N., Kawahara, A., Yamaguchi, A., Nishi, T.
-
Journal Title
J.Biol.Chem
Volume: 286
Pages: 1758-1766
Related Report
Peer Reviewed
-
[Journal Article] Macrophage Abca5influences cellular cholesterol efflux and increases susceptibility to atheroscrosis in female Ldlr knockout mice2010
Author(s)
Ye, D., Meurs, I., Ohigashi, M., Zhao, Y., Kubo, Y., Yamaguchi A, van Beckel, T.J.C., Nishi T. and van Eck, M
-
Journal Title
Biochem. Biophys. Res. Commun
Volume: 395
Pages: 387-394
Related Report
Peer Reviewed
-
[Journal Article] Macrophage Abca5 influences cellular cholesterol efflux and increases susceptibility to atheroscrosis in female Ldlr knockout mice.2010
Author(s)
Ye, D., Meurs, I., Ohigashi, M., Zhao, Y., Habets, K.LL., Calpe-Berdiel, L., Kubo, Y., Yamaguchi, A, van Beckel, T.J.C., Nishi, T., van Eck, M.
-
Journal Title
Biochem.Biophys.Res.Commun.
Volume: 395
Pages: 387-394
Related Report
Peer Reviewed
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
