The significance of lysophosphatidic acid in vascular biology and application of its measurement into laboratory medicine

• Project/Area Number: 16390162
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: The University of Tokyo
• Principal Investigator: YATOMI Yutaka The University of Tokyo, Faculty of Medicine, Professor, 医学部附属病院, 教授 (60200523)
• Co-Investigator(Kenkyū-buntansha): HIGASHI Katsumi The University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (50159109) ; NAKAHARA Kazuhiko The University of Tokyo, Faculty of Medicine, Professor, 医学部附属病院, 教授 (70101095)
• Project Period (FY): 2004 – 2005
• Project Status: Completed (Fiscal Year 2005)
• Budget Amount: ¥6,000,000 (Direct Cost: ¥6,000,000); Fiscal Year 2005: ¥2,900,000 (Direct Cost: ¥2,900,000); Fiscal Year 2004: ¥3,100,000 (Direct Cost: ¥3,100,000)
• Keywords: lysophosphatidic acid / lysophospholipid / laboratory test / vascular endothelial cell / plasma / autotaxin / vascular biology / flowcytometry

Research Abstract

In this research project, the significance of LPA in vascular biology and clinical application of the measurement of LPA have been pursued, as follows.
1.The elucidation of signal transduction mechanisms of LPA receptor, i.e., LPAx, in platelets and vascular endothelial cells
2.Clinical application of the measurement of LPA and lysoPLD/autotaxin
The plasma preparation method for LPA measurement was determined, and the reference range for plasma LPA was set. However, the concentration of LPA increased dramatically just under incubation while the serum lysoPLD activity was relatively stable. Based on the results on within-run and between-run precision, interference, detection limit, and linearity, it was considered that the lysoPLD assay can be applied to clinical laboratory testing. The serum lysoPLD activity in healthy female subjects (3.84 ± 0.62 nmol/ml/min) was significantly higher than that in the male subjects (3.24 ± 0.54 nmol/ml/min). We feel the lysoPLD assay method seems to be promising for laboratory testing.
3.LPA metabolism in the blood
The LPA metabolism is dynamic in the blood steam. The plasma LPA levels are balanced by its production by lysoPLD from LPC and degradation by lipid phosphate phosphatase. Furthermore, the biological activities of LPA may be determined by relative expression of LPAx and lipid phosphate phosphatase on target cells.
4.The analysis of lysoPLD/ATX and LPAx expression on various cells
This has been performed mainly on hematopoietic cells. The expression of lysoPLD/ATX seems to vary during hematopoietic differentiation.
5.The significance of measurement of LPA and lysoPLD in the plasma/serum samples from chronic liver diseases

Research Products

• [Journal Article] Sphingosine 1-phosphate in vascular biology : possible therapeutic strategies to control vascular diseases. (2006)
  • Author(s): Yatomi, Y.
  • Journal Title: Curr. Pharm. Des. 12 Pages: 575-587
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] A new nethod for assessment of an anti-5HT(2A) agent, sarpogrelate hydrochloride, on platelet aggregation. (2006)
  • Author(s): Satoh, K. ほか
  • Journal Title: J Thromb Haemost. 4 Pages: 479-481
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Sphingosine 1-phosphate in vascular biology : possible therapeutic strategies to control vascular diseases. (2006)
  • Author(s): Yatomi, Y.
  • Journal Title: Curr.Pharm.Des. 12 Pages: 575-587
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A new method for assessment of an anti-5HT(2A) agent, sarpogrelate hydrochloride, on platelet aggregation. (2006)
  • Author(s): Satoh, K., Yatomi, Y., Ozaki, Y.
  • Journal Title: J Thromb Haemost 4 Pages: 479-481
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A new method for assessment of an anti-5HT(2A) agent, sarpogrelate hydrochloride, on platelet aggregation. (2006)
  • Author(s): Satoh, K.ほか
  • Journal Title: J Thromb Haemost. 4 Pages: 479-481
• [Journal Article] The herbal medicine inchin-ko-to (TJ-135) induces apoptosis in cultured rat hepatic stellate cells. (2006)
  • Author(s): Ikeda, H.ほか
  • Journal Title: Life Sci. (印刷中)
• [Journal Article] Sphingosine 1-phosphate-related metabolism in the blood vessel. (2005)
  • Author(s): Aoki, S. ほか
  • Journal Title: J. Biochem. 138 Pages: 47-55
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Platelet release of beta-thrmboglobulin an dplatelet factor 4 and serotonin in plasma samples. (2005)
  • Author(s): Ohkawa, R. ほか
  • Journal Title: Clin. Biochem. 38 Pages: 1023-1026
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] The intracellular action of sphingosine 1-phosphate in GPVI-mediated Ca^2; mobilization in platelets. (2005)
  • Author(s): Ohmori, T. ほか
  • Journal Title: Thromb. Res. 115 Pages: 409-415
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Sphingosine 1-phosphate-related metabolism in the blood vessel. (2005)
  • Author(s): Aoki, S., Yatomi, Y., Ohta, M., Osada, M., Kazama, F., Satoh, K., Nakahara, K., Ozaki, Y.
  • Journal Title: J.Biochem. 138 Pages: 47-55
  • NAID: 10017346110
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Platelet release of beta-thromboglobulin and platelet factor 4 and serotonin in plasma samples. (2005)
  • Author(s): Ohkawa, R., Hirowatari, Y., Nakamura, K., Ohkubo, S., Ikeda, H., Okada, M., Tozuka, M., Nakahara, K., Yatomi, Y.
  • Journal Title: Clin.Biochem. 38 Pages: 1023-1026
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] The intracellular action of sphingosine 1-phosphate GPVI-mediated Ca2+ mobilization in platelets. (2005)
  • Author(s): Ohmori, T., Yatomi, Y., Osada, M.Ozaki, Y.
  • Journal Title: Thromb.Res. 115 Pages: 409-415
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Sphingosine 1-phosphate-related metabolism in the blood vessel. (2005)
  • Author(s): Aoki S.ほか
  • Journal Title: J.Biochem. 138 Pages: 47-55
• [Journal Article] Platelet release of beta-thromboglobulin and platelet factor 4 and serotonin in plasma samples. (2005)
  • Author(s): Ohkawa, R.ほか
  • Journal Title: Clin.Biochem. 38 Pages: 1023-1026
• [Journal Article] The intracellular action of sphingosine 1-phsphate in GPVI-mediated Ca2+ mobilization in platelets. (2005)
  • Author(s): Ohmori, T.ほか
  • Journal Title: Thromb.Res. 115 Pages: 409-415
• [Journal Article] Platelet-derived sphingosine 1-phosphate induces contraction of coronary artery smooth muscle cells via S1P2. (2004)
  • Author(s): Ohmori, T. ほか
  • Journal Title: Thromb. Haemost. 2 Pages: 203-205
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Independence of tumor necrosis factor-alpha-induced adhesion molecule expression from sphingosine 1-phosphate signaling in vascular endothelial cells. (2004)
  • Author(s): Miura, Y. ほか
  • Journal Title: J. Thromb. Haemost. 2 Pages: 1019-1021
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Clear visual detection of circulating platelet aggregates in acute myocardial infarction using a flow cytometer equipped with an imaging device. (2004)
  • Author(s): Satoh, K. ほか
  • Journal Title: Platelets 15 Pages: 61-62
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Cleavage of platelet endothelial cell adhesion molecule-1 (PECAM-1) in platelets exposed to high shear stress. (2004)
  • Author(s): Naganumu, Y. ほか
  • Journal Title: J. Thromb. Haemost. 2 Pages: 1998-2008
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Sphingosine 1-phosphate inhibits migration of RBL-2H3 cells via S1P2 : cross-talk between platelets and mast cells. (2004)
  • Author(s): Yokoo, E. ほか
  • Journal Title: J. Biochem. 135 Pages: 673-681
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Expression of ceramide kinase in hematopoietic cells. (2004)
  • Author(s): Yokota, H. ほか
  • Journal Title: Eur. J. Haematol. 73 Pages: 307-308
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Sphingosine 1-phosphate breakdown in platelets. (2004)
  • Author(s): Yatomi, Y. ほか
  • Journal Title: J. Biochem. 136 Pages: 495-502
  • NAID: 10016202913
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Usefulness of CD9 detection in the diagnosis of acute megakaryoblastic leukemia. (2004)
  • Author(s): Yatomi, Y. ほか
  • Journal Title: Eur. J. Haematol. 72 Pages: 229-230
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Platelet-derived sphingosine 1-phosphate induces contraction of coronary artery smooth muscle cells via S1P2. (2004)
  • Author(s): Ohmori, T., Yatomi, Y., Osada, M., Ozaki, Y.
  • Journal Title: J.Thromb.Haemost. 2 Pages: 203-205
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Independence of tumor necrosis factor-alpha-induced adhesion molecule expression from sphingosine 1-phosphate signaling in vascular endothelial cells. (2004)
  • Author(s): Miura, Y., Yatomi, Y., Ohmori, T., Osada, M., Ozaki, Y.
  • Journal Title: J.Thromb.Haemost. 2 Pages: 1019-1021
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Clear visual detection of circulating platelet aggregates in acute myocardial infarction using a flow cytometer equipped with an imaging device. (2004)
  • Author(s): Satoh, K., Yatomi, Y., Osada, T., Takeda, S., Tsuyuguchi, N., Kubota, F., Ozaki, Y.
  • Journal Title: Platelets 15 Pages: 61-52
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Cleavage of platelet endothelial cell adhesion molecule-1 (PECAM-1) in platelets exposed to high shear stress. (2004)
  • Author(s): Naganuma, Y., Satoh, K., Yi, Q., Asazuma, N., Yatomi, Y., Ozaki, Y.
  • Journal Title: J.Thromb.Haemost. 2 Pages: 1998-2008
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Sphingosine 1-phosphate inhibits migration of RBL-2H3 cells via S1P2 : cross-talk between platelets mast cells. (2004)
  • Author(s): Yokoo, E., Yatomi, Y., Takafuta, T., Osada, M., Okamoto, Y., Ozaki, Y.
  • Journal Title: J.Biochem. 135 Pages: 673-681
  • NAID: 130003534710
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Expression of ceramide kinase in hematopoietic cells. (2004)
  • Author(s): Yokota, H., Yatomi, Y., Mashige, F., Nakahara, K.
  • Journal Title: Eur.J.Haematol. 73 Pages: 307-308
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Sphingosine 1-phosphate breakdown in platelets. (2004)
  • Author(s): Yatomi, Y., Yamamura, S., Hisano, N., Nakahara, K., Igarashi, Y., Ozaki, Y.
  • Journal Title: J.Biochem. 136 Pages: 495-502
  • NAID: 10016202913
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Usefulness of CD9 detection in the diagnosis of acute megakaryoblastic leukemia. (2004)
  • Author(s): Yatomi, Y., Yoneyama, A., Nakahara, K.
  • Journal Title: Eur.J.Haematol. 72 Pages: 229-230
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] The herbal medicine inchin-ko-to (TJ-135) induces apoptosis in cultured rat hepatic stellate cells.
  • Author(s): Ikeda, H. ほか
  • Journal Title: Life Sci. (印刷中)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] The herbal medicine inchin-ko-to (TJ-135) induces apoptosis in cultured rat hepatic stellate cells.
  • Author(s): Ikeda, H., Nagashima, K., Yanase, M., Tomiya, T., Arai, M., Inoue, Y., Tejima, K., Nishikawa, T., Watanabe, N., Kitamura, K., Isono, T., Yahagi, N., Noiri, E., Inao, M., Mochida, S., Kume, Y., Yatomi, Y., Nakahara, K., Omata, M., Fujiwara, K.
  • Journal Title: Life Sci. (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Book] Sphingolipid Biology の中のSphingosine 1-phosphate-related metabolism in the blood vessel. (2006)
  • Author(s): Yatomi, Y. ほか
  • Publisher: Springer-Verlag(印刷中)
  • Description: 「研究成果報告書概要(和文)」より
• [Book] Spbingosin 1-phosphate-related metabolism in the blood vessel.(Sphingolipid Biology)(eds., Y.Hirabayashi, Y.Igarashi, A.H.Merrill, Jr.) (2006)
  • Author(s): Yatomi, Y., Aoki, S., Igarashi, Y.
  • Publisher: Springer-Verlag, Tokyo.(in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Book] Sphingolipid Biologyの中のSphingosine 1-phosphate-related metabolism in the blood vessel. (2006)
  • Author(s): Yatomi, Y.ほか
  • Publisher: Springer-Verlag(印刷中)