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

溶血磷脂酸在血管生物学中的意义及其测量在检验医学中的应用

• 批准号: 16390162
• 负责人: YATOMI Yutaka
• 金额: $ 3.84万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390162/
• 关键词: lysophosphatidic acid; lysophospholipid; laboratory test; vascular endothelial cell; plasma; autotaxin; vascular biology; flowcytometry

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 cells2.Clinical application of the measurement of LPA and lysoPLD/autotaxinThe 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 bloodThe 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 cellsThis 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

本研究项目对LPA在血管生物学中的意义以及LPA测量的临床应用进行了如下探讨：1.阐明LPA受体LPAx在血小板和血管内皮细胞中的信号转导机制2.LPA和lysoPLD/autotaxin测量的临床应用LPA的血浆制备方法 测定结果，并设定血浆LPA的参考范围。然而，LPA 浓度在孵化过程中急剧增加，而血清 lysoPLD 活性相对稳定。根据批内和批间精密度、干扰、检出限和线性的结果，认为lysoPLD检测可应用于临床实验室检测。健康女性受试者血清lysoPLD活性（3.84±0.62nmol/ml/min）显着高于男性受试者（3.24±0.54nmol/ml/min）。我们认为lysoPLD检测方法对于实验室检测似乎很有前景。3.血液中的LPA代谢LPA代谢在血液蒸汽中是动态的。血浆 LPA 水平通过 LPC 中 lysoPLD 的产生和脂质磷酸酶的降解来平衡。此外，LPA的生物活性可以通过LPAx和脂质磷酸酶在靶细胞上的相对表达来确定。4.lysoPLD/ATX和LPAx在各种细胞上的表达分析主要是在造血细胞上进行的。 lysoPLD/ATX的表达似乎在造血分化过程中发生变化。5.慢性肝病血浆/血清样本中LPA和lysoPLD测定的意义

项目成果

Spbingosin 1-phosphate-related metabolism in the blood vessel.(Sphingolipid Biology)(eds., Y.Hirabayashi, Y.Igarashi, A.H.Merrill, Jr.)

血管中与鞘氨醇 1-磷酸相关的代谢。（鞘脂生物学）（编辑，Y.Hirabayashi，Y.Igarashi，A.H.Merrill，Jr.）

• 发表时间: 2006
• 作者: Yatomi;Y.;Aoki;S.;Igarashi;Y.
• 通讯作者: Y.

The herbal medicine inchin-ko-to (TJ-135) induces apoptosis in cultured rat hepatic stellate cells.

• DOI: 10.1016/j.lfs.2005.09.024
• 发表时间: 2006-04
• 期刊: Life sciences
• 影响因子: 6.1
• 作者: H. Ikeda;K. Nagashima;M. Yanase;T. Tomiya;M. Arai;Y. Inoue;Kazuaki Tejima;Takako Nishikawa;N. Watanabe;Kazuya Kitamura;Tomomi Isono;N. Yahagi;E. Noiri;M. Inao;S. Mochida;Yukio Kume;Y. Yatomi;K. Nakahara;M. Omata;K. Fujiwara

Platelet-derived sphingosine 1-phosphate induces contraction of coronary artery smooth muscle cells via S1P2.

血小板衍生的 1-磷酸鞘氨醇通过 S1P2 诱导冠状动脉平滑肌细胞收缩。

• 发表时间: 2004
• 期刊: Thromb. Haemost. 2
• 作者: Ohmori;T. ほか
• 通讯作者: T. ほか

Independence of tumor necrosis factor-alpha-induced adhesion molecule expression from sphingosine 1-phosphate signaling in vascular endothelial cells.

肿瘤坏死因子-α 诱导的粘附分子表达与血管内皮细胞中 1-磷酸鞘氨醇信号传导的独立性。

• 发表时间: 2004
• 期刊: J. Thromb. Haemost. 2
• 作者: Miura;Y. ほか
• 通讯作者: Y. ほか

The intracellular action of sphingosine 1-phsphate in GPVI-mediated Ca2+ mobilization in platelets.

1-磷酸鞘氨醇在 GPVI 介导的血小板 Ca2+ 动员中的细胞内作用。

• 发表时间: 2005
• 期刊: Thromb.Res. 115
• 作者: Ohmori;T.ほか
• 通讯作者: T.ほか