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1996 Fiscal Year Final Research Report Summary

Development of new drug for intractable hyperlipidemia and its clinical application

Research Project

Project/Area Number 07557073
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section試験
Research Field 内分泌・代謝学
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

KITA Toru  Kyoto University, Graduate School of Medicine, Professor, 医学研究科, 教授 (60161460)

Co-Investigator(Kenkyū-buntansha) ISHII Kenji  Kyoto University, Graduate School of Medicine, Instructor, 医学研究科, 助手 (00212811)
WAKATSUKI Yoshio  Kyoto University, Graduate School of Medicine, Lecturer, 医学研究科, 講師 (40220826)
KUME Noriaki  Kyoto University, Graduate School of Medicine, Instructor, 医学研究科, 助手 (20252455)
YOKODE Masayuki  Kyoto University, Graduate School of Medicine, Lecturer, 医学研究科, 講師 (20252447)
DOI Toshio  Kyoto University, Graduate School of Medicine, Lecturer, 医学研究科, 講師 (60183498)
Project Period (FY) 1995 – 1996
KeywordsCholesterol / Apo B-protein / MTP / VLDL / CHO-cell / Hepatocytes / HSP-70 / Transgenic mouse
Research Abstract

We found apolipoprotein B-100 (apo B) secretion is regulated in response to the change of intracellular cholesteryl ester contents by adding low density lipoprotein (LDL). LDL caused a significant dose-dependent increase in apo B secretion, because of preventing the degradation of apo-B protein itself. Immediately after apo B protein is translated from mRNA of apo B,microsomal triglyceride transfer protein (MTP) makes assembly with apo B protein. As a result, VLDL particles are formed. Therefore MTP plays an important role for regulating VLDL production and secretion. To investigate this regulation, we first cloned full length of cDNA for MTP,succeeded to transfect MTP cDNA to CHO cells and detected MTP protein. We are now doing following experiments.
1) To establish MTP overexpression system in rabbit hepatocytes.
2) To establish transgenic mouse which over express MTP cDNA using transferin promoter.
3) To analyze proteins which could regulate post-translational modification of apo-B protein, suchi as MTP,HDP-70 and unknown protein.

  • Research Products

    (40 results)

All Other

All Publications (40 results)

  • [Publications] Tanaka, M. et al.: "Regulation of apolipoprotein B secretion in hepatocytes from Watanabe heritable hyperlipidemic rabbit, an animal model of familial hypercholesterolemia." Aherosclerosis. 114. 73-82 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ochi, H. et al.: "Elevated levels of cyclic AMP inhibits protein kinase-C independent mechanisms of endothelial PDGF-B chain and ICAN-1 gene induction by lysophosphatidylcholine" Circulation Research. 77. 530-535 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kita, T. et al.: "Lessons concerning human lipoprotein metabolism from the study of the WHHL rabbit." Atherosclerosis. X. 111-113 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Uematsu, M. et al.: "Coexistent myelodysplastic syndrome and non-Hodgkin lymphoma. Report of a case and review of the literature." Int. J. Hematology. 62. 45-51 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kume, N. et al.: "Involvement of protein kinase C-independent mechanisms in endothelial ICAM-1 up-regulation by lysophosphatidylcholine." Ann. N. Y. Acad. Sci.748. 541-542 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Komatsu, T. et al.: "Lipoprotein glomerulopathy with a new apolipoprotein E phenotype" Am. J. Kidney Diseases. 25. 952-953 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nishida, R. et al.: "Endoscopic Sclerotherapy in a Rat Model of Esophageal Varices" Scand J. Gastroenterol. 30. 489-496 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Dekigai, H. et al.: "Mechanism of Helicobacter pylori-Associated Gastric Mucosal Injury" Digestive Diseases and Sciences. 40. 1332-1339 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Teramoot, T. et al.: "Clinical Efficacy of fluvastatin for hyperlipidemia in Japanese patients." Am. J. Cardiol.76. 33A-36A (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yokode, M. et al.: "The macrophage and its role in atherogenesis" Internal Medicine. 34. 281-283 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yokode, M. et al.: "cigarette smoke and lipoprotein modification : a possible interpretation for development of atherosclerosis." Ann. N. Y. Acad. Sci.748. 294-301 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Iehara, N. et al.: "Differentiation of smooth muscle phenotypes in mouse mesangial cells." Kid. Int.49. 1330-1341 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Iehara, N. et al.: "Advanced glycosylation endoproducts modulate transcriptional regulations of type IV collagen and α-smooth muscle actin on mesangial cells." Nephrology. 118. 141-146 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Uematsu-Yanagita, M. et al.: "Microscopic polyarteritis during polymyalgia rheumatica remission." Am. J. Kid. Dis.28. 289-291 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Yokode, M. et al.: "Modification of high-and low-density lipoproteins by cigarette smoke oxidants." The Ann. N. Y. Acad. Sci.786. 245-251 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kita, T. et al.: "Lysophosphatidylcholine induced gene expression of endothelial platelet-derived growth factor-b-chain and intercellular adbesion molecule-1" Medical Science Symposia Series. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kita, T. et al.: "Induction of endothelial platelet-derived growth factor-b-chain and intercellular adhesion molecule-1 by lysophosphatibylcholine" The Ann. N. Y. Acad. Sci.(in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sakai, A. et al.: "P-selectin and vascular cell adhesion molecule-1 are focally expressed in aortas of hypercholesterolemic rabbits prior to intimal accumulation of Macrophages and T-lymphocytes." Arterioscler Thromb Vasc Biol.17. 310-316 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nishi, E. et al.: "Lysophosphatidylcholine increases expression of heparin-binding epidermal growth factor-like growth factor in human T-lymphocytes." Circulation Research. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sawamura, T. et al.: "Anovel endothelial receptor for oxidized LDL" Nature. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tanaka, M., Otani, H., Yokode, M.& Kita, T.: "Regulation of apolipoprotein B secretion in hepatocytes from Watanabe heritable hyperlipidemic rabbit, an animal model of familial hypercholesterolemia." Atherosclerosis. 114. 73-82 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ochi, H., Kume, N., Nishi, E.& Kita, T.Elevated: "levels of cyclic AMP inhibits protein kinase-C independent mechanisms of endothelial PDGF-B chain and ICAM-1 gene induction by lysophosphatidylcholine." Circulation Research. 77. 530-535 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kita, T., Tanaka, M., Otani, H., Kume, N.& Yokode, M.: "Lessons concerning human lipoprotein metabolism from the study of the WHHL rabbit." Atherosclerosis. X. 111-113 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Uematsu, M., Ochi, H., Ueda, Y., Hakamata, Y., Yokode, M., Yoshida, Y.& Kita, T.: "Coexistent myelodysplastic syndrome and non-Hodgkin lymphoma. Report of a case and review of the literature." Int.J.Hematology. 62. 45-51 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kume, N., Ochi, H., Nishi, E., Gimbrone, M.A.& Kita, T.: "Involvement of protein kinase C-independent mechanisms in endothelial ICAM-1 up-regulation by lysophosphatidylcholine." Ann.N.Y.Acad.Sci.748. 541-542 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Komatsu, T., Kanatsu, K., Ochi, H., Kita, T.& Doi, T.: "Lipoprotein glomerulopathy with a new apolipoprotein E phenotype." Am.J.Kidney Diseases. 25. 952-953 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishida, R., Inoue, Y., Takimoto, H., Hamashima, H.& Kita, T.: "Endoscopic Sclerotherapy in a Rat Model of Esophageal Varices." Scand J.Gastroenterol. 30. 489-496 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Dekigai, H., Murakami, M.& Kita, T.: "Mechanism of Helicobacter pylori-Associated Gastric Mucosal Injury." Digestive Diseases and Sciences. 40. 1332-1339 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Teramoto, T., Goto, Y., Kurokawa, K., Nakamura, H., Yoshida, S., Saito, Y., Nakaya, N., Itakura, H., Takaku, F., Yamada, N., Hata, Y., Kuzuya, F., Mabuchi, H., Kita, T., Tarui, S., Matsuzawa, Y., Yamamoto, A., Tsushima, M., Kajiyama, G., Arakawa, K.& Ishioka, T.: "Clinical Efficacy of fluvastatin for hyperlipidemia in Japanese patients." Am.J.Cardiol. 76. 33A-36A (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yokode, M.& Kita, T.: "The macrophage and its role in atherogenesis." Internal Medicine. 34. 281-283 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yokode, M.Nagano, Y., Arai, H., Ueyama, K., Ueda, Y.& Kita, T.: "Cigarette smoke and lipoprotein modification : a possible interpretation for development of atherosclerosis." Ann.N.Y.Acad.Sci.748. 294-301 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Iehara, N.Takeoka, H., Tsuji, H., Imabayashi, T., Foster, D.N., Strauch, A.R., Yamada, Y., Kita, T.& Doi, T.: "Differentiation of smooth muscle phenotypes in mouse mesangial cells." Kid, Int.49. 1330-1341 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Iehara, N., Takeoka, H., Yamada, Y., Kita, T.& Doi, T.: "Advanced glycosylation endoproducts modulate transcriptional regulations of type IV collagen and alpha- smooth muscle actin on mesangial cells." Nephrology. 118. 141-146 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Uematsu-Yanagita, M., Cho, M., Hakamata, Y., Tanaka, M., Ishii, K.Kume, N., Ochi, H., Wakatsuki, Y., Yokode, M., Murakami, M., Yoshioka, H., Doi, T.& Kita, T.: "Microscopic polyarteritis during polymyalgia rheumatica ramission." Am.J.Kid.Dis.28. 289-291 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yokode, M., Ueyama, K., Nagano, Y., Arai, H., Ueda, Y.& Kita, T.: "Modification of high- and low-density lipoproteins by cigarette smoke oxidants." The Ann.N.Y.Acad.Sci.786. 245-251 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kita, T., Kume, N., Ochi, H., Nishi, E., Nagano, Y.& Yokode, M.: "Lysophosphatidylcholine induced gene expression of endothelial platelet-derived growth factor-b-chain and intercellular adhesion molecule-1." Medical Science Symposia Series. (in press.).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kita, T., Kume, N., Ochi, H., Nishi, E., Sakai, A., Ishii, K., Nagano, Y.& Yokode, M.: "Induction of endothelial platelet-derived growth factor-b-chain and intercellular adhesion molecule-1 by lysophosphatidylcholine." The Ann.N.Y.Acad.Sci.(in press.).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sakai, A., Kume, N., Nishi, E., Tanoue, K., Miyasaka, M.& Kita, T.: "P-selectin and vascular cell adhesion molecule-1 are focally expressed in aortas of hypercholesterolemic rabbits prior to intimal accumulation of Macrophages and T-lymphocytes." Arteriosclerosis, Thrombosis, and Vascular Biology. 17. 310-316 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nishi, E., Kume, N., Ochi, H., Moriwaki, H., Wakatsuki, Y., Higashiyama, S., Taniguchi, N.& Kita, T.: "Lysophosphatidylcholine increases expression of heparin-binding epidermal growth factor-like growth factor in human T-lymphocytes." Circulation Research. (in press.).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sawamura, T., Kume, N., Aoyama, T., Moriwaki, H., Hoshikawa, H., Aiba, Y., Tanaka, T., Miwa, S., Katsura, Y., Kita, T.& Masaki, T.: "A novel endothelial receptor for oxidized LDL." Nature. (in press.).

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-03-09  

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