Study on the endoplasmic stress induced by oxsterol ester and its implication to diseases

• Project/Area Number: 22390187
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Jichi Medical University
• Principal Investigator: ISHIBASHI Shun 自治医科大学, 医学部, 教授 (90212919)
• Co-Investigator(Kenkyū-buntansha): OOSUGA Junniti 自治医科大学, 医学部, 准教授 (10334400) ; YAGYU Hiroaki 自治医科大学, 医学部, 准教授 (60348018)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000); Fiscal Year 2012: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2011: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2010: ¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000)
• Keywords: 小胞体ストレス / 細胞死 / マクロファージ / コレステロール / オキシステロール / 脂質代謝異常 / ERストレス / NCEH1 / アポトーシス / ACAT

Research Abstract

NCEH1、an microsomal protein which hydrolizes cholesterol ester (CE), mediates the hydrolysis of esterified form of 25-hydroxycholesterol (25-HC), one of oxysterols. In human monocyte-derived macrophages, NCEH1 is responsible for the CE hydrolysis. Absence

Research Products

• [Journal Article] Macrophage lipoprotein lipase modulates the development of atherosclerosis but not adiposity (2013)
  • Author(s): Takahashi M, Yagyu H, Tazoe F, Nagashima S, Ohshiro T, Okada K, Osuga J, Goldberg IJ, Ishibashi S.
  • Journal Title: J Lipid Res Volume: 54(4) Issue: 4 Pages: 1124-34
  • DOI: 10.1194/jlr.m035568
  • Peer Reviewed
• [Journal Article] Liver-specific deletion of 3-hydroxy-3-methylglutaryl coenzyme A reductase causes hepatic steatosis and death. (2012)
  • Author(s): Nagashima S, Yagyu H, Ohashi K, Tazoe F, Takahashi M, Ohshiro T, Bayasgalan T, Okada K, Sekiya M, Osuga J, Ishibashi S.
  • Journal Title: Arterioscler Thromb Vasc Biol. Volume: 32(8) Issue: 8 Pages: 1824-31
  • DOI: 10.1161/atvbaha.111.240754
  • Peer Reviewed
• [Journal Article] Interleukin-17 deficiency reduced vascular inflammation and development of atherosclerosis in Western diet-induced apoE-deficient mice (2012)
  • Author(s): F.Usui
  • Journal Title: Biochem Biophys Res Commun Volume: 420 Issue: 1 Pages: 72-77
  • DOI: 10.1016/j.bbrc.2012.02.117
  • Peer Reviewed
• [Journal Article] Depot-specific expression of lipolytic genes in human adipose tissues-association among CES1 expression, triglyceride lipase activity and adiposity. (2011)
  • Author(s): Nagashima S, Yagyu H, Takahashi N, Kurashina T, Takahashi M, Tsuchita T, Tazoe F, Wang XL, Bayasgalan T, Sato N, Okada K, Nagasaka S, Gotoh T, Kojima M, Hyodo M, Horie H, Hosoya Y, Okada M, Yasuda Y, Fujiwara H, Ohwada M, Iwamoto S, Suzuki M, Nagai H, Ish
  • Journal Title: J Atheroscler Thromb. Volume: 18(3) Pages: 190-9
• [Journal Article] an acyl-coenzyme A:cholesterol acyltransferase 2-selective inhibitor, attenuates hypercholesterolemia and atherosclerosis in murine models of hyperlipidemia. (2011)
  • Author(s): Ohshiro T, Matsuda D, Sakai K, Degirolamo C, Yagyu H, Rudel LL, Omura S, Ishibashi S, Tomoda H. Pyripyropene A
  • Journal Title: Arterioscler Thromb Vasc Biol. Volume: 31(5) Issue: 5 Pages: 1108-15
  • DOI: 10.1161/atvbaha.111.223552
  • Peer Reviewed
• [Journal Article] Depot-specific expression of lipolytic genes in human adipose tissues--association among CES1 expression, triglyceride lipase activity and adiposity. (2011)
  • Author(s): Nagashima S
  • Journal Title: J Atheroscler Thromb Volume: 18 Pages: 190-9
  • Peer Reviewed
• [Journal Article] The role of neutral cholesterol ester hydrolysis in macrophage foam cells. (2011)
  • Author(s): Sekiya M
  • Journal Title: J Atheroscler Thromb Volume: 18 Pages: 359-64
  • Peer Reviewed
• [Journal Article] Abrogation of neutral cholesterol ester hydrolytic activity causes adrenal enlargement. (2011)
  • Author(s): Ohta K
  • Journal Title: Biochem Biophys Res Commun. Volume: 404 Pages: 254-260
  • Peer Reviewed
• [Journal Article] Depot-Specific Expression of Lipolytic Genes in Human Adipose Tissues. (2011)
  • Author(s): Nagashima S
  • Journal Title: J Atheroscler Thromb. Volume: 18 Pages: 190-199
  • Peer Reviewed
• [Journal Article] The critical role of neutral cholesterol ester hydrolase 1 in cholesterol removal from human macrophages (2010)
  • Author(s): Igarashi M, Kadowaki T
  • Journal Title: Circ. Res Volume: 107 Issue: 11 Pages: 1387-1395
  • DOI: 10.1161/circresaha.110.226613
• [Journal Article] Abrogation of neutral cholesterol ester hydrolytic activity causes adrenal enlargement (2010)
  • Author(s): Ohta K, Sekiya M, Uozaki H, Igarashi M, Takase S, Kumagai M, Takanashi M, Takeuchi Y, Izumida Y, Kubota M, Nishi M, Okazaki H, Iizuka Y, Yahagi N, Yagyu H, Fukayama M, Kadowaki T, Ohashi K, Ishibashi S, Osuga JI
  • Journal Title: Biochem Biophys Res Commun Volume: 404 Issue: 1 Pages: 254-60
  • DOI: 10.1016/j.bbrc.2010.11.103
  • Peer Reviewed
• [Journal Article] The critical role of neutral cholesterol ester hydrolase 1 in cholesterol removal from human macrophages. (2010)
  • Author(s): Igarashi M
  • Journal Title: Circ Res. Volume: 107 Pages: 1387-1395
  • Peer Reviewed
• [Presentation] Macrophage lipoprotein lipase modulates the development of atherosclerosis but not adiposity.
  • Author(s): Takahashi M
  • Organizer: American Diabetes Association 72nd Scientific Session
  • Place of Presentation: フィラデルフィア
  • Invited
• [Presentation] In vivo efficacy of PRD017, a new pyripyropene A derivative and highly potent ACAT2-selective inhibitor, in apolipoprotein E KO mice
  • Author(s): Ohshiro T
  • Organizer: American Heart Association Scientific Session 2012
  • Place of Presentation: ロサンゼルス
  • Invited
• [Presentation] Marked inhibition of atherosclerosis in mice lacking HMG-CoA reductase in a macrophage-specific manner
  • Author(s): Tumenbayar B
  • Organizer: American Heart Association Scientific Session 2012
  • Place of Presentation: オーランド