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Expression of adhesion molecules and growth factors in vascular endothelial cell

Research Project

Project/Area Number 08670788
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

KUME Noriaki (1997-1998)  Kyoto University, Faculty of Medicine, Lecturer, 医学研究科, 講師 (20252455)

越智 弘 (1996)  京都大学, 医学研究科, 助手 (80204220)

Co-Investigator(Kenkyū-buntansha) 久米 典昭  京都大学, 医学研究科, 助手 (20252455)
Project Period (FY) 1996 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1998: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1997: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1996: ¥700,000 (Direct Cost: ¥700,000)
KeywordsAtherosclerosis / endothelial cells / lysophosphatidylcholine / MAP kinases / tyrosine phosphorylation / PECAM-1 / チロシニリン酸化 / PECANM-1 / 接着分子 / atherosclerosis / endothelial cells / lysophosphatidylcholine / tyrosine phosphorylation
Research Abstract

Endothelial-leukocyte adhesion molecules such as VCAM-1 and ICAM-1, have been implicated in recruitment of circulating monocytes and T-lymphocytes to atherosclerotic lesions. In addition, smooth muscle growth factors, including PDGF A and B chains and HB-EGF, appear to play crucial role in migration and proliferation of medical smooth muscle cells into atherosclerotic intima. Lysophosphatidylcholine (Ox-LDL), can transcriptionally induce expression of VCAM-1, ICAM-1, PFGF, and HB-EGF in cultured vascular endothelial cells; therefore, we sought to define transcriptional and sibnal transduction mechanisms involved in lyso-PC-induced expression. We have found that elevated levels of intracelluar cyclic AMP inhibited lyso-PC-induced expression of PDGF and ICAM-1. Furthermore, lyso-PC-induced expression of PDGF was dependent upon protein tyrosine phosphorylation. We, therefore, explored the protein that can rapidly phosphorylated in the tyrosine residue. We revealed that a protein with a molecular mass of 130kDa, which was designated p130, was rapidly and transiently tyrosine phosphorylated by lyso-PC. By use of immunoblotting and immunoprecipitation, we have identified p130 as PECAM-1 which was expressed on the intercellular junction of cultured endothelial cells. Our study also have demonstrated that MAP kinases, such as ERK and JNK, were activated by lyso-PC, which appeared to depend upon protein tyrosine phosphorylation.

Report

(4 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • 1996 Annual Research Report
  • Research Products

    (28 results)

All Other

All Publications (28 results)

  • [Publications] Hiroshi Ochi,Noriaki Kume,et al: "Tyrosine phosphorylation of platelet endothelial cell adhesion molecule-1 induced by lysophosphatidylcholine in cultured endothelial cells"Eiochem.Biophys.Res.Commun. vol.243. 862-868 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Eiichiro Nishi,Noriaki Kume,et al: "Lysophosphatidylcholine enhances cytokine-induced interferon gamma expression in human T lymphocytes"Circulation Research. vol.83. 508-515 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Noriaki Kume,Takatoshi Murase,et al: "Inducible expression of lectin-like oxidized LDL receptor-1 in vascular endothelial cells"Circulation Research. vol.83. 322-327 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takatoshi Murase,Noriaki Kume,et al: "Fluid shear stress transcriptionally induces lectin-like oxidized LDL receptor-1 in vascular endothelial cells"Circulation Research. vol.83. 328-333 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hideaki Moriwaki,Noriaki Kume,et al: "Ligand specificity of LOX-1,a novel endothelial receptor for oxidized low density lipoprotein"Arterioscler.Thromb.Vasc.Biol. vol.18. 1541-1547 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Eiichiro Nishi, Noriaki Kume, Hiroshi Ochi, Hideaki Moriwaki, Shigeki Higashiyama, Naoyuki Taniguchi, Toru Kita: "Lysophosphtidylcholine induces heparin-binding epidermal growth factor-like growth factor and interferon-γ in human T-lymphocytes."Ann.N.Y.Acad.Sci. 811. 519-524 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Atsushi Sasaki, Noriaki Kume, Eiichiro Nishi, Kenjiro Tanoue, Masayuki Miyasaka, Toru Kita: "P-selection and vascular cell adhesion molecule-1 are focally expressed in aortas of hypercholesterolemic rabbits before intimal accumulation of macrophages and Tlymphocytes."Arterioscler. Thromb. Vasc. Biol. 17. 310-316 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tatsuya Sawamura, Noriaki Kume, Takuma Aoyama, Hideaki Moriwaki, Hajime Hoshikawa, Yuichi Aiba, Takeshi Tanaka, Soichi Miwa, Yoshimoto Katsura, Toru Kita, Tomoh Masaki: "An endothelial receptor for oxidized low-density lipoprotein"Nature. 386. 73-77 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Eiichiro Nishi, Noriaki Kume, Hiroshi Ochi, Hideaki Moriwaki, Yoshio Wakutsuki, Shigeki Higashiyma, Shigeki Higashiyama, Naoyuki Taniguchi, Toru Kita: "Lysophosphatidycholine increases expression of heparin-binding epidermal growth factor-like growth factor in human Tlymphocytes."Circ.Res... 80. 638-644 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hiroshi Ochi, Noriaki Kume, Eiichiro Nishi,m Hideaki Moriwaki, Michitaka Masuda, Keigi Fujiwara, Toru Kita: "Tyrosine phosphorylation of platelet endothelial cell adhesion molecule-1 induced by lysophosphatidylcholine in cultured endothelial cells."Biochem.Biophys.Res.Commun.. 243. 862-868 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Eiichiro Nishi, Noriaki Kume, Yasushi Ueno, Hiroshi Ochi, Hideaki Moriwaki, Toru Kita: "Lysophosphatidylcholine enhances cytokine-induced interferon gamma expression in human Tlymphocytes."Circ.Res... 83. 508-515 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Noriaki Kume, Takatoshi Murase, Hideaki Moriwaki, Takuma Aoyama, Tatsuya Sawamura, Tomoh Masaki, Toru Kita: "inducible expression of lectin-like oxidized LDL receptor-1 in vascular endothelial cells."Circ.Res. 83. 322-327 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takatoshi Murase, Noriaki Kume, Risa Korenaga, Joji Ando, Tatsuya Sawamura, Tomoh Masaki, Toru Kita: "Fluid shear stress transcriptionally induces lectin-like oxidized LDLreceptor-1 in vascular endothelial cells."Circ.Res.. 83. 328-333 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hideaki Moriwaki, Noriaki Kume, Tatsuya Sawamura, Takuma Aoyama, Hajime Hoshikawa, Hiroshi Ochi, Eiichiro Nishi, Tomoh Masaki, Toru Kita: "Ligand specificity of lOX-1, a novel endothelial receptor for oxidized low density lipoprotein."Arterioscler.Thromb.Vasc.Biol. 18. 1541-1547 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hideaki Moriwaki, Noriaki Kume, Hiroharu Kataoka, Takatoshi Murase, Eiichiro Nishi, Tatsuya Sawamura, Tomoh Masaki, Toru Kita: "Expression of lectin-like oxidized low density lipoprotein receptor-1 in human and murine macrophages-upregulated expression by TNF-a"FEBS Lett.. 440. 29-32 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shizuka Sakata-Kaneko, Yoshio Wakatsuki, Takashi Usui, Yoichi Matsunaga, Toshiyuki Itoh, Eiichiro Nishi, Noriaki Kume, Toru Kita: "Lysophosphatidylcholine upregulates CD40L expression in newly activated human CD4+ Tcells."FEBS Lett. 433. 161-165 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Harunobu Ozaki, Kenji Ishii, Hidenori Akira, Noriaki Kume, Toru Kita: "Lysophosphatidylcholine activates mitogen-activated protein kinases by a tyrosine kinase-dependent pathway in bovine aortic endothelial cells."Atherosclerosis. 143. 261-266 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hiroshi Ochi,Noriaki Kume,et al: "Tyrosine phosphorylation of platelet endothelial cell adhesion molecule-1 induced by lysophosphatidylcholine in cultured endothelial cells" Biochem.Biophys.Res.Commun.vol.243. 862-868 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Eiichiro Nishi,Noriaki KUme,et al: "Lysophosphatidylcholine enhances cytokine-induced interferon gamma expression in human T lymphocytes" Circulation Research. vol.83. 508-515 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Noriaki Kume,Takatoshi Murase,et al: "Inducible expression of lectin-like oxidized LDL receptor-1 in vascular endothelial cells." Circulation Research. vol.83. 322-327 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Takatoshi Murase,Noriaki Kume,et al: "Fluid shear stress transcriptionally induces lectin like oxidized LDL receptor-1 in vascular endothelial cells." Circulation Research. vol.83. 328-333 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hideaki Moriwaki,Noriaki Kume,et al: "Ligand specificity of LOX-1,a novel endothelial receptor for oxidized low density lipoprotein." Arterioscler.Thromb.Vasc.Biol.vol.18. 1541-1547 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Eiichiro Nishi, Noriaki Kume, et al: "Lysophosphtidylcholine induces heparin-binding epidermal growth facter-like growth facter and interferon-γ in human T-lymphocytes." Annals of New York Academy of Sciences. 811. 519-524 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Atsushi Sakai, Noriaki Kume et al: "P-selectin and vascular cell adhesion molecule-1 are focally expressed in aortas of hypercholesterolemic rabbits before intimal accumulation of macrophages and T lymphocyte" Arteriosclerosis Thrombosis and Vascular Biology. 17. 310-316 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tatsuya Sawamura, Noriaki Kume et al: "An endothelial receptor for oxidized low-density lipoprotein." Nature. 386. 73-77 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Eiichiro Nishi, Noriaki Kume et al: "Lysophosphatidycholine increases expression of heparin-binding epidermal growth factor-like growth factor in human T lymphocytes." Circulation Research. 80. 638-644 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hiroshi Ochi, Noriaki Kume et al: "Tyrosine phosphorylation of platelet endothelial cell adhesion molecule-1 induced by lysophosphatidylcholine in cultured endothelial cells" Biochemical and Biophysical Research Communications. 243. 862-868 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ochi H,Kume N,Nishi E,Kato T: "Elevated levels of cyclic AMP inhibits protein kinase C-independent mechanisms of endothelial PDGF-B chain and ICAM-1 gene induction by lysophosphatidy lcholine" Circulation Research. 77. 530-535 (1995)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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