Molecular mechanism of ATP-dependent transporters involvedinl in lipid homeostasis in brain
Project/Area Number |
16380070
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Applied biochemistry
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Research Institution | Kyoto University |
Principal Investigator |
UEDA Kazumitsu Kyoto University, Division of Applied Life Sciences, Professor (10151789)
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Project Period (FY) |
2004 – 2007
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Project Status |
Completed (Fiscal Year 2007)
|
Budget Amount *help |
¥16,270,000 (Direct Cost: ¥15,400,000、Indirect Cost: ¥870,000)
Fiscal Year 2007: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2006: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2005: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2004: ¥4,900,000 (Direct Cost: ¥4,900,000)
|
Keywords | brain / cholesterol / ABC proteins / lipids / transporters / lifestyle associated diseases / Alzheimer disease / sphingomyelin / ABCA1 / ABCG1 / HDL / ABCタンパク質 / アルツハイマー病 / 膜蛋白質 / 自己免疫疾患 / ATPase / α1-シントロフィン |
Research Abstract |
Molecular mechanism of ATP-dependent transporters involved in lipid homeostasis in brain was investigated 1) Functional analysis of ABCA1. ABCA1 plays a major role in cholesterol homeostasis in our body and brain. However, the mechanisms is still not clear. To explore the mechanism of ABCA1-mediated HDL formation, we expressed human ABCA1 in insect Sf9 cells and purified it. Purified ABCA1 showed robust ATPase activity when reconstituted in liposomes made of synthetic phosphatidylcholine. The results suggest that the ATPase activity of ABCA1 is stimulated preferentially by phospholipids with choline head groups, phosphatidylcholine and sphingomyelin. 2) The effects of the cellular sphingomyelin level on HDL formation by ABCA1. When sphingomyelin content was reduced, apoA-I-dependent cholesterol efflux by ABCA1 increased 1.65-fold. Exogenously added sphingomyelin significantly reduced the apoA-I-dependent efflux of cholesterol. 3) Functional analysis of ABCG1. We have shown that ABCG1 mediates the efflux of not only cholesterol but also sphingomyelin (SM) and phosphatidylcholine. We examined whether it plays an important role in the ABCG1-mediated efflux of cholesterol. The results suggest that the ABCG1-mediated efflux of cholesterol and SM is dependent on the cellular SM level and distribution of cholesterol in the plasma membrane.
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Report
(5 results)
Research Products
(80 results)
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[Journal Article] Bile Salt-Dependent Efflux of Cellular Phospholipids Mediated by ATP Binding Cassette Protein B4.2007
Author(s)
Morita, S.-y. Kobayashi, A., Takanezawa, Y., Kioka, N., Handa, T., Arai, H., Matsuo, M., Ueda, K.
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Journal Title
Hepatology, 46
Pages: 188-199
Description
「研究成果報告書概要(和文)」より
Related Report
Peer Reviewed
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[Journal Article] Enhanced apoA-I-dependent cholesterol efflux by ABCA1 from sphingomyelin-deficient CHO cells.2007
Author(s)
Nagao, K., Takahashi, K., Hanada, K., Kioka, N., Matsuo, M., and Ueda, K.,
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Journal Title
J Biol Chem. 282
Pages: 14868-74
Description
「研究成果報告書概要(和文)」より
Related Report
Peer Reviewed
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[Journal Article] Modulation of drug-stimulated ATPase activity of human MDR1/P-glycoprotein by cholesterol.2007
Author(s)
Kimura, Y., Kioka, N., Kato, H., Matsuo, M., Ueda, K.
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Journal Title
Cancer Sci. 98,
Pages: 1303-1310
Description
「研究成果報告書概要(和文)」より
Related Report
Peer Reviewed
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[Journal Article] Sphingomyelin-dependence of cholesterol efflux mediated by ABCG12007
Author(s)
Sano, O., Kobayashi, A., Nagao, K., Kumagai, K., Kioka, N., Hanada, K., Ueda, K., Matsuo, M
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Journal Title
J Lipid Res 48(11)
Pages: 2377-84
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Bile Salt-Dependent Efflux of Cellular Phospholipids Mediated by ATP Binding Cassette Protein B42007
Author(s)
Morita, S.-y., Kobayashi, A., Takanezawa, Y., Kioka, N., Handa, T., Arai, H., Matsuo, M., Ueda, K
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Journal Title
Hepatology 46
Pages: 188-199
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Enhanced apoA-I-dependent cholesterol efflux by ABCA1 from sphingomyelin-deficient CHO cells2007
Author(s)
Nagao, K., Takahashi, K., Hanada, K., Kioka, N., Matsuo, M., Ueda, K
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Journal Title
J Biol Chem 282
Pages: 14868-74
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Efflux of sphingomyelin, cholesterol and phosphatidylcholine by ABCG1.2006
Author(s)
Kobayashi, A., Takanezawa, Y., Hirata, T., Shimizu, Y., Misasa, K., Kioka, N., Arai, H., Ueda, K., and Matsuo, M.
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Journal Title
J Lipid Res. 47,
Pages: 1791-1802
Description
「研究成果報告書概要(和文)」より
Related Report
Peer Reviewed
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[Journal Article] Serum amyloid A generates high density lipoprotein with cellular lipid in an ABCA1-or ABCA7-dependent manner.2006
Author(s)
Abe-Dohmae, S., Kato, K. H., Kumon, Y., Hu, W., Ishigami, H., Iwamoto, N., Okazaki, M., Wu, C. A., Tsujita, M., Ueda, K. and Yokoyama, S.
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Journal Title
J Lipid Res. 47,
Pages: 1542-1550
Description
「研究成果報告書概要(和文)」より
Related Report
Peer Reviewed
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[Journal Article] Efflux of sphingomyelin, cholesterol and phosphatidylcholine by ABCG12006
Author(s)
Kobayashi, A., Takanezawa, Y., Hirata, T., Shimizu, Y., Misasa, K., Kioka, N., Arai, H., Ueda, K., Matsuo, M
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Journal Title
J Lipid Res 47
Pages: 1791-1802
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Serum amyloid A generates high density lipoprotein with cellular lipid in an ABCA1- or ABCA7-dependent manner2006
Author(s)
Abe-Dohmae, S., Kato, K.H., Kumon, Y., Hu, W., Ishigami, H., Iwamoto, N., Okazaki, M., Wu, C.A., Tsujita, M., Ueda, K., Yokoyama, S
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Journal Title
J Lipid Res 47
Pages: 1542-1550
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Detection of ABCA7-positive cells in salivary glands from patients with Sjogren's syndrome.2005
Author(s)
Toda, Y., Aoki, R., Ikeda, Y., Azuma, Y., Kioka, N., Matsuo, M., Sakamoto, M., Mori, S., Fukumoto, M., and Ueda, K.
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Journal Title
Pathol. Int. 55,
Pages: 639-643
NAID
Description
「研究成果報告書概要(和文)」より
Related Report
Peer Reviewed
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[Journal Article] Cloning of ABCA17, anovel, rodent sperm-specific ATP-binding cassette(ABC)transporter that regulates intracellular lipid metabolism.2005
Author(s)
Ban, N., Sasaki, M., Sakai, H., Ueda, K., and Inagaki, N.
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Journal Title
Biochem J 389
Pages: 577-585
Description
「研究成果報告書概要(和文)」より
Related Report
Peer Reviewed
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[Journal Article] Fenofibric acid, an active form of fenofibrate, increases apolipoprotein A-l-mediated high-density lipoprotein biogenesis by enhancing transcription of ATP-binding cassette transporter A1 gene in a liver X receptor-dependent manner.2005
Author(s)
Arakawa, R., Tamehiro, N., Nishimaki-Mogami, T., Ueda, K., and Yokoyama, S.
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Journal Title
Arterioscler Thromb Vasc Biol 25
Pages: 1193-1197
Description
「研究成果報告書概要(和文)」より
Related Report
Peer Reviewed
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[Journal Article] Detection of ABCA7-positive cells in salivary glands from patients with Sjogren's syndrome2005
Author(s)
Toda, Y., Aoki, R., Ikeda, Y., Azuma, Y., Kioka, N., Matsuo, M., Sakamoto, M., Mod, S., Fukumoto, M., Ueda, K
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Journal Title
Pathol. Int 55
Pages: 639-643
NAID
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Cloning of ABCA17, a novel, rodent sperm-specific ATP-binding cassette (ABC) transporter that regulates intracellular lipid metabolism2005
Author(s)
Ban, N., Sasaki, M., Sakai, H., Ueda, K., Inagaki, N
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Journal Title
Biochem 389
Pages: 577-585
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Fenofibric acid, an active form of fenofibrate, increases apolipoprotein A-I-mediated high-density lipoprotein biogenesis by enhancing transcription of ATP-binding cassette transporter Al gene in a liver X receptor-dependent manner2005
Author(s)
Arakawa, R., Tamehiro, N., Nishimaki-Mogami, T., Ueda, K., Yokoyama, S
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Journal Title
Arterioscler Thromb Vasc Biol 25
Pages: 1193-1197
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Human ABCA3, a product of a responsible gene for abca3 for fatal surfactant deficiency in newborns, exhibits unique ATP hydrolysis activity and generates intracellular multilamellar vesicles,2004
Author(s)
Nagata, K., Yamamoto, A., Ban, N., Tanaka, AR., Matsuo, M., Kioka, N., Inagaki, N., and Ueda, K.
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Journal Title
Biochem Biophys Res Commun, 324
Pages: 262-268
Description
「研究成果報告書概要(和文)」より
Related Report
Peer Reviewed
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[Journal Article] α1-syntrophin modulates turnover of ABCA1.2004
Author(s)
Munehira, Y., Qhnishi, T., Kawamoto, S., Furuya, A., Shitara, K., Imamura, M., Yokota, T., Takeda, S. i., Amachi, T., Matsuo, M., Kioka, N. and Ueda, K.
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Journal Title
J Biol Chem 279
Pages: 15091-15095
Description
「研究成果報告書概要(和文)」より
Related Report
Peer Reviewed
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[Journal Article] Verapamil Increases the Apolipoprotein-Mediated Release of Cellular Cholesterol by Induction of ABCA1 Expression via an LXR-lndependent Mechanism.2004
Author(s)
Suzuki, S., Nishimaki-Mogami, T., Tamehiro, N., Inoue, K., Arakawa, R., Abe-Dohmae, S., Tanaka, A. R., Ueda, K. and Yokoyama, S.
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Journal Title
Arterioscler Thromb Vasc Biol 24
Pages: 519-525
Description
「研究成果報告書概要(和文)」より
Related Report
Peer Reviewed
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[Journal Article] Microanalysis for MDR1 ATPase by high-performance liquid chromatography with a titanium dioxide column.2004
Author(s)
Kimura, Y., Shibasaki, S., Morisato, K., Ishizuka, N., Minakuchi, H., Nakanishi, K., Matsuo, M., Amachi, T., Ueda, M. and Ueda, K.
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Journal Title
Anal. Biochem 326
Pages: 262-266
Description
「研究成果報告書概要(和文)」より
Related Report
Peer Reviewed
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[Journal Article] Human ABCA7 supports apolipoprotein-mediated release of cellular cholesterol and phospholipid to generate HDLA.2004
Author(s)
Abe-Dohmae, S., Ikeda, Y., Matsuo, M., Hayashi, M., Okuhira, K. I., Ueda, K., and Yokoyama, S.
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Journal Title
J Biol Chem 279(1)
Pages: 604-11
Description
「研究成果報告書概要(和文)」より
Related Report
Peer Reviewed
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[Journal Article] Human ABCA3, a product of a responsible gene for abca3 for fatal surfactant deficiency in newborns, exhibits unique ATP hydrolysis activity and generates intracellular multilamellar vesicles2004
Author(s)
Nagata, K., Yamamoto, A., Ban, N., Tanaka, AR., Matsuo, M., Kioka, N., Inagaki, N., Ueda, K
-
Journal Title
Biochem Biophys Res Commun 324
Pages: 262-268
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] a1-syntrophin modulates turnover of ABCA12004
Author(s)
Munehira, Y., Ohnishi, T., Kawamoto, S., Furuya, A., Shitara, K., Imamura, M., Yokota, T., Takeda, S.i., Amachi, T., Matsuo, M., Kioka, N., Ueda, K
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Journal Title
J Biol Chem 279
Pages: 15091-15095
Description
「研究成果報告書概要(欧文)」より
Related Report
-
[Journal Article] Verapamil Increases the Apolipoprotein-Mediated Release of Cellular Cholesterol by Induction of ABCA1 Expression via an LXR-Independent Mechanism2004
Author(s)
Suzuki, S., Nishimaki-Mogami, T., Tamehiro, N., Inoue, K., Arakawa, R., Abe-Dohmae, S., Tanaka, A.R., Ueda, K., Yokoyama, S
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Journal Title
Arterioscler Thromb Vasc Biol 24
Pages: 519-525
Description
「研究成果報告書概要(欧文)」より
Related Report
-
[Journal Article] Microanalysis for MDR1 ATPase by high-performance liquid chromatography with a titanium dioxide column2004
Author(s)
Kimura, Y., Shibasaki, S., Morisato, K., Ishizuka, N., Minakuchi, H., Nakanishi, K., Matsuo, M., Amachi, T., Ueda, M., Ueda, K
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Journal Title
Anal. Biochem 326
Pages: 262-266
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Human ABCA7 supports apolipoprotein-mediated release of cellular cholesterol and phospholipid to generate HDLA2004
Author(s)
Abe-Dohmae, S., Ikeda, Y., Matsuo, M., Hayashi, M., Okuhira, K.I., Ueda, K., Yokoyama, S
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Journal Title
J Biol Chem 279(1)
Pages: 604-11
Description
「研究成果報告書概要(欧文)」より
Related Report
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