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Molecular Basis of Intracellular Cholesterol Homeostasis

Research Project

Project/Area Number 12557095
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Metabolomics
Research InstitutionNagoya City University

Principal Investigator

YOKOYAMA Shiniji  Nagoya City University Medical School, Professor, 医学部, 教授 (10142192)

Co-Investigator(Kenkyū-buntansha) TSUJITA Maki  Nagoya City University Medical School, Research Associate, 医学部, 助手 (10253262)
DOHMAE Sumiko (ABE Sumiko)  Nagoya City University Medical School, Assistant Professor, 医学部, 講師 (70227700)
ITO Jinichi  Nagoya City University Medical School, Associate Professor, 医学部, 助教授 (60167260)
AOTSUKA Tomoshi  Grelan Pharmaceutical Co. Ltd., Manager, 化学研究グループ, 課長
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥13,000,000 (Direct Cost: ¥13,000,000)
Fiscal Year 2001: ¥5,200,000 (Direct Cost: ¥5,200,000)
Fiscal Year 2000: ¥7,800,000 (Direct Cost: ¥7,800,000)
Keywordscholesterol / lipoprotein / HDL / apolipoprotein / cell membrane / リポタンパク質 / アポリポタンパク質 / ABCA1 / カペオリン
Research Abstract

During the current grant term, research accomplishment is summarized below for the mechanism and physiological relevance of HDL assembly by apolipoprotein-cell interaction. Inhibition of the HDL assembly reaction by an HDL-lowering drug probucol was reproduced in mice in vivo, and demonstrated the this reaction is a main source of plasma HDL (BBA 1485 : 199, 2000) and the main organ for the reaction is the liver (ATVB 21, 394, 2001). Assembly of HDL in mouse monocytic leukemia cell RAW 264 is induced by cAMP in parallel with physical binding of apolipoprotein to the cell, and with 10-tome increase of abca1 mRNA (Biochemistry 39, 11092, 2000). From the experiments with THP-1 cells and fibroblasts, it was revealed that ABCA1 is not absolute requirement for the HDL assembly, that caveolin-1 plays an important role in incorporation of cholesterol into the HDL, and that progesterone inhibits this pathway by an unknown mechanism (JLR 41, 1952, 2000 ; JBC277, 7929, 2002 ; BBA 1532, 173, 2001). Membrane raft was suggested to be a site for the HDL assembly (JLR41, 894, 2000). When ABCA1 is transfected and functionally expressed in HEK293, the protein was shown with a signal peptide cleaved and the N-terminal exposed to outside (BBRC 283, 1019, 2001). A part of the results above is summarized in a review article (BBA 1529, 231, 2000).

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (49 results)

All Other

All Publications (49 results)

  • [Publications] Jin-ichi Ito, et al.: "Cholesterol-sphingomyelin interaction in membrane and apolipoprotein-mediated cellular cholesterol efflux"J. Lipid Res.. 41. 894-904 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Maki Tsujita, et al.: "Apolipoprotein-mediated cellular cholesterol/phospholipid efflux and plasma high density lipoprotein level in mice"Biochim.Biophys.Acta. 1485. 199-213 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Koon K.Teo, et al.: "Long term effects of cholesterol lowering and angiotensin-converting enzyme inhibition on coronary atherosclerosis : The Simvastatin/Enalapril Coronary Atherosclerosis Trial (SCAT)"Circulation. 102. 1748-1754 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sumiko Abe-Dohmae, et al.: "Characterization of apolipoprotein-mediated HDL generation induced by cAMP in a murine macrophage cell line"Biochemistry. 39. 11092-11099 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Reijiro Arakawa, et al.: "Involvement of caveolin-1 in cholesterol-enrichment of HDL during its assembly by apolipoprotein and THP-1 cells"J. Lipid Res. 41. 1952-1962 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shogo Suzuki, et al.: "Enhancement of the cAMP-induced apolipoprotein A-I-mediated cellular lipid release by calmodulin inhibitors W7 and W5 from RAW264 mouse macrophage cell line cells"J. Cardiovasc. Pharmacol. 36. 609-616 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shinji Yokoyama: "Release of cellular cholesterol: Molecular mechanism for cholesterol homeostasis in cells and in the body"Biochim. Biophys. Acta. 1529. 231-244 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Li-Yong Zhang, et al.: "Cholesterol homeostasis in rat astrocytoma cells GA-1"J. Biochem. 128. 837-845 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shigehiro Tomimoto, et al.: "Effect of probucol in lecithin-cholesterol acyltransferase deficient mice : Inhibition of two independent cellular cholesterol releasing pathways in vivo"Arterioscler. Thromb. Vasc. Biol.. 21. 394-400 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Akitomo Goto, et al.: "Cholesteryl ester transfer protein and atherosclerosis in Japanese subjects : A study based on coronary angiography"Atheroscelrosis. 159. 153-163 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kazuhisa Kojima, et al.: "Progesterone Inhibits Apolipoprotein-mediated cellular lipid release : A putative mechanism for the decrease of HDL"Biochim. Biophys. Acta. 1532. 173-184 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Arowu R.Tanaka, et al.: "Human ABCA1 contains a large amino-terminal extracellular domain homologous to an epitope of Sjogren's syndrome"Biochem. Biophys. Res. Commun.. 283. 1019-1025 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kuniko Okumura-Noji, et al.: "Cholesteryl Ester Transfer Protein-Deficiency Causes Slow Egg Embryonation of Schistosoma japonicum"Biochem. Biophys. Res. Commun. 286. 305-310 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Qianqian Li, et al.: "Active taurocholic acid flux through hepatoma cells increases the cellular pool of unesterified cholesterol derived from lipoproteins"Biochim. Biophys. Acta. 1580. 22-30 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Jin-ichi Ito, et al.: "Apolipoprotein A-I induces translocation of cholesterol, phospholipid and caveolin-1 to cytosol in rat astrocytes"J. Biol. Chem. 277. 7929-7935 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sachiko Ueno, et al.: "An Acidic Fibroblast Growth Factor-Like Factor Secreted into the Brain Cell Culture Medium Upregulates ApoE Synthesis, HDL Secretion and Cholesterol Metabolism in Rat Astrocytes"Biochim. Biopys. Acta. (in press). (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Jinichi Ito, Yuko Nagayasu and Shinji Yokoyama: "Cholesterol-sphingomyelin interaction in membrane and apolipoprotein-mediated cellular cholesterol efflux"J. Lipid Res.. 41. 894-904 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Maki Tsujita, Shigehiro Tomimoto, Kuniko Okuyama-Noji, Mitsuyo Okazaki and Shinji Yokoyama: "Apolipoproteinmediated cellular cholesterol/phospholipid efflux and plasma high density lipoprotein level in mice"Biochim. Biophys. Acta. 1485. 199-213 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Koon K,Teo, Jeffrey R. Burton, Christopher E. Sutler, Sylvain Plante, Daine Catellier, Wayne Tymchak, Vladimir Dzavik, Dylan Taylor, Shinji Yokoyama, and Terrence J.: "Montague on behalf of the SCAT investigators. Long term effects of cholesterol lowering and angiotensin-converting enzyme inhibition on coronary atherosclerosis : The Simvastatin/Enalapril Coronary Atherosclerosis Trial (SCAT)"Circulation. 102. 1748-1754 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sumiko Abe-Dohmae, Shogo Suzuki, Youichiro Wada, Hiroyuki Aburatani, Dennis E. Vance, and Shinji Yokoyama: "Characterization of apoiipoprotein-mediated HDL generation induced by cAMP in a murine macrophage cell line"Biochemistry. 39. 11092-11099 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Reiiiro Arakawa, Sumiko Abe-Dohmae, Michiyo Asai, Jinichi Ito. and Shinji Yokoyama: "Involvement of caveolin-1 in cholesterol-enrichment of HDL during its assembly by apolipoprotein and THP-1 cells"J. Lipid Res.. 41. 1952-1962 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shogo Suzuki, Sumiko Abe-Dohmae, Tatsuya Fukutomi, Shigenori Ito, Makoto Itoh and Shinji Yokoyama: "Enhancement of the cAMP-induced apolipoprotein A-l-mediated cellular lipid release by calmodulin inhibitors W7 and W5 from RAW264 mouse macrophage cell line cells"J. Cardiovasc. Pharmacol.. 36. 609-616 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shinji Yokoyama: "Release of cellular cholesterol : Molecular mechanism for cholesterol homeostasis in cells and in the body"Biochim. Biophy. Acta. 1529. 231-244 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Li-Yong Zhang, Jin-ichi Ito, Taiji Kato and Shinji Yokoyama: "Cholesterol homeostasis in rat astrocytoma cells GA-1"J. Biochem.. 128. 837-845 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shigehiro Tomimoto, Maki Tsujita, Mitsuyo Okazaki, Shin-ichi Usui, Toyohiro Tada, T. Fukutomi, Shigenori Ito, Makoto Itoh and Shinji Yokoyama: "Effect of probucol in lecithin-cholesterol acyltransferase deficient mice : Inhibition of two independent cellular cholesterol releasing pathways in vivo"Arterioscier. Thromb. Vasc. Biol.. 21. 394-400 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Akitomo Goto, Kanna Sasai, Shogo Suzuki, Tatsuya Fukutomi, Shigenori Ito, Toyoaki Matsushita, Mitsuhiro Okamoto, Takahiko Suzuki, Makoto Itoh, Kuniko Okuyama-Noji, and Shinji Yokoyama: "Cholesteryl ester transfer protein and atherosclerosis in Japanese subjects : A study based on coronary angiography"Atheroscelrosis. 159. 153-163 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kazuhisa Kojima, Sumiko Abe-Dohmae, Reijiro Arakawa, Isamu Murakami, Kaoru Suzumori and Shinji Yokoyama: "Progesterone Inhibits Apolipoprotein-mediated cellular lipid release : A putative mechanism for the decrease of HDL"Biochim. Biophys. Acta. 1532. 173-184 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Arowu R. Tanaka, Yuika Ikeda, Sumiko Abe-Dohmae, Reijiro Arakawa, Keishi Sadanami, Akinori Kidera, Satoshi Nakagawa, Takahiro Nagase, Ryo Aoki, Noriyuki Kioka, Teruo Amachi, Shinji Yokoyama and Kazumitsu Ueda: "Human ABCA1 contains a large amino-terminal extracellular domain homologous to an epitope of Sjogren's syndrome"Biochim. Biophys. Res. Commun.. 283. 1019-1025 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kuniko Okumura-Noji, Kanna Sasai, Renii Zhan, Hitoshi Kawaguchi, Haruhiko Maruyama, Toyohiro Tada, Hikaru Takahashi, Mitsuyo Okazaki, Takashi Miida, Nagahiko Sakuma, Genjiro Kimura, Nobuo Ohta, and Shinji Yokoyama: "Choiesteryl Ester Transfer Protein-Deficiency Causes Slow Egg Embryonation of Schistosoma japonicum"Biochem. Biophys. Res. Commun.. 286. 305-310 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Qianqian Li, Shinji Yokoyama, Luis B. Agellon.: "Active taurocholic acid flux through hepatoma cells increass the cellular pool of unesterlified cholesterol derived from lipoproteins"Biochim. Biophys. Acta. 1580. 22-30 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shigehiro Tomimoto, et al.: "Effect of probucol in lecithin-cholesterol acyltransferase deficient mice: Inhibition of two independent cellular cholesterol releasing nathwavs in vivo. Arterioscier"Thromb. Vasc. Biol.. 21. 394-400 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Akitomo Goto, et al.: "Cholesteryl ester transfer protein and atherosclerosis in Japanese subjects: A study base on coronary angiography"Atherosceirosis. 159. 153-163 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kazuhisa Kojima, et al.: "Progesterone Inhibits Apolipoprotein-mediated cellular lipid release: A putative mechanism for the decrease of HDL"Biochim. Biophys. Acta. 1532. 173-184 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Arowu R.Tanaka, et al.: "Human ABCA1 contains a large amino-terminal extracellular domain homologous to an epitope of Sjogren's syndrome"Biochem. Biophys. Res. Commun.. 283. 1019-1025 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kuniko Okumura-Noji, et al.: "Cholesteryl Ester Transfer Protein-Deficiency Causes Slow Egg Embryonation of Schistosoma japonicum"Biochem. Biophys. Res. Commun.. 256. 305-310 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Qianqian Li, et al.: "Luis B. Agellon. Active taurocholic acid flux through hepatoma cells increases the cellular pool of unesterified cholesterol derived from lipoproteins"Biochim. Biophys. Acta. 1580. 22-30 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Jin-ichi Ito, et al.: "Apolipoprotein A-I induces translocation of cholesterol, phospholipid and caveolin-1 to cvtosol in rat astrocytes"J. Biol. Chem.. 277. 7929-7935 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sachiko Ueno, et al.: "An Acidic Fibroblast Growth Factor-Like Factor Secreted into the Brain Cell Culture Medium Upregulates ApoE Synthesis, HDL Secretion and Cholesterol Metabolism in Rat Astrocytes"Biochim. Biopys. Acta. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Jin-ichi Ito and Shinji Yokoyama.: "Sialosylcholesterol induces reorganization of astrocyte filament network."Biochim.Biophys.Acta. 1495. 195-202 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Jin-ichi Ito, et al: "Cholesterol-sphingomyelin interaction in membrane and apolipoprotein-mediated cellular cholesterol efflux."J.Lipid Res.. 41. 894-904 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Maki Tsujita, et al: "Apolipoprotein-mediated cellular cholesterol/phospholipid efflux and plasma high density lipoprotein level in mice."Biochim.Biophys.Acta. 1485. 199-213 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Koon K.Teo, et al.: "Montague on behalf of the SCAT investigators.Long term effects of cholesterol lowering and angiolensin-converling enzyme inhibition on coronary atherosclerosis : The Simyaslatin/Enalapril Coronary Atheroscierosis Trial (SCAT)."Circulation. 102. 1748-1754 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Sumiko Abe-Dohmae, et al.: "Characterization of apolipoprotien-mediated HDL generation induced by cAMP in a murine macrophage cell line."Biochemistry. 39. 11092-11099 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Reijiro Arakawa, et al: "Involvement of caveolin-1 in cholesterol-enrichment of HDL during its assembly by apolipoprotein and THP-1 cells."J.Lipid Res.. 41. 1952-1962 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shogo Suzuki, et al: "Enhancement of the cAMP-induced apolipoprotein A-1-mediated cellular lipid release by calmodulin inhibitors W7 and W5 from RAW 264 mouse macrophage cell line cells."J.Cardiovasc.Pharmacol.. 36. 609-616 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shinji Yokoyama.: "Release of cellular cholesterol : Molecular mechanism for cholesterol homeostasis in cells and in the body."Biochim.Biophys.Acta. 1529. 231-244 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Li-Yong Zhang,Jin-ichi Ito,Taiji Kato and Shinji Yokoyama.: "Cholesterol homeostasis in rat astrocytoma cells GA-1."J.Biochem.. 128. 837-845 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shigehiro Tomimoto, et al: "Effect of probucol in lecithin-cholesterol acyltransferase deficient mice : Inhibition of two independent cellular cholesterol releasing pathways in vivo."Arterioscler.Thromb.Vasc.Biol.. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Akitomo Goto, et al: "Cholesteryl ester transfer protein and atherosclerosis in Japanese subjects : A study based on coronary angiography."Atheroscelrosis. (in press). (2001)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2021-11-29  

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