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Lipid Mediators and Lipid Metaborome

脂质介质和脂质代谢组

基本信息

批准号：
15002004
负责人：
SHIMIZU Takao
金额：
$ 443.46万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Specially Promoted Research
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2006
项目状态：
已结题

项目摘要

1 Functional analysis of lysophospholipid acyltransferase ; We identified several lysophospholipid acyltransferases involving in the remodeling pathway of membrane lipids biosynthesis by in silico database analyses. Based on these information, we succeeded in molecular cloning of lyso-PAF acetyltransferase and LPCAT1. Lyso-PAF acetyltransferase is a critical enzyme in stimulus dependent formation of PAR LPCAT1 is an acetyltransferase involving in synthesis of phosphatidylcholine in pulmonary surfactant and play a pivotal role in respiratory physiology. We are generating gene-deficient mice of these enzymes to clarify the physiological importance. We further analyze other enzymes in this family.2 Functional analysis of phospholipase A_2 (PLA_2) ; Among many mammalian PLA_2s, cytosolic PLA_2 α(cPLA_2α) plays a critical role in various physiological and pathophysiological conditions through generating lipid mediators. We newly discovered cPLA_2 family enzymes, cPLA_2δ, cPLA_2ε, and cPLA_2 … More ζ . We are analyzing the physiological function of these enzymes.3 Identification of novel lipid mediator receptors (G-protein coupled receptors : GPCRs) ; To search for novel lipid mediator receptors among approx. 150 orphan GPCRs, we succeeded in selecting approx. 30 candidate GPCRs. In these GPCRs, we have newly identified TDAG8 and G2A as proton-sensing receptors and LPA4 as a lysophosphatidic acid receptor. We are continuously performing the ligand screening for other orphan GPCRs.4 Analysisi of GPCR-deficient mice ; To clarify the physiological significance of lipid mediator GPCRs, we have generated genedeficient mice for BLT1, BLT2, CysLT2 and LPA4. In the analysis of BLT1-deficient mice, we obtained evidence that BLT1 is necessary for production of Th2 cytokines and the development of airway hyperresponsiveness in an OVA-induced bronchial asthma model.5 High throughput quantitation of lipid mediators by LC-MS ; By the combination of lipid chromatography and tandem mass spectrometry (MS/MS), we developed a highly specific and reasonably sensitive assay procedure to simultaneously quantitate > 14 different mediators in 10 min single run. Less

溶血磷脂酰基转移酶的功能分析；我们通过计算机数据库分析确定了几种溶血磷脂酰基转移酶参与膜脂生物合成的重塑途径。基于这些信息，我们成功克隆了lyso-PAF乙酰转移酶和LPCAT1。Lyso-PAF乙酰转移酶是刺激依赖性PAR形成的关键酶LPCAT1是一种乙酰转移酶，参与肺表面活性物质磷脂酰胆碱的合成，在呼吸生理中起关键作用。我们正在培养具有这些酶的基因缺陷小鼠，以阐明其生理重要性。我们进一步分析了该家族的其他酶磷脂酶A_2 （PLA_2）功能分析在哺乳动物的许多PLA_2s中，细胞质PLA_2α (cPLA_2α)通过生成脂质介质在各种生理和病理生理条件中起着关键作用。我们新发现了cPLA_2家族酶，cPLA_2δ， cPLA_2ε和cPLA_2…More ζ。我们正在分析这些酶的生理功能新型脂质介质受体（g蛋白偶联受体：gpcr）的鉴定目的：在近50种植物中寻找新的脂质介质受体。150个孤儿gpcr，我们成功地选择了大约。30个候选gpcr。在这些gpcr中，我们新发现TDAG8和G2A是质子感应受体，LPA4是溶血磷脂酸受体。我们正在继续进行其他孤儿gpcr的配体筛选gpcr缺陷小鼠的分析为了阐明脂质介质gpcr的生理意义，我们培育了BLT1、BLT2、CysLT2和LPA4基因缺陷小鼠。在对BLT1缺失小鼠的分析中，我们获得证据表明，在ova诱导的支气管哮喘模型中，BLT1是Th2细胞因子产生和气道高反应性发展所必需的脂质介质的LC-MS高通量定量研究通过脂质层析和串联质谱（MS/MS）的结合，我们开发了一种高特异性和合理灵敏度的检测方法，可以在10分钟内同时定量> 14种不同的介质。少

项目成果

期刊论文数量（105）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Cytosolic phospholipase A2 alpha-deficient mice are resistant to experimental autoimmune encephalomyelitis.

缺乏实验性自身免疫性脑脊髓炎的胞质磷脂酶A2α缺陷型小鼠具有抗性。

DOI：
10.1084/jem.20050665
发表时间：
2005-09-19
期刊：
JOURNAL OF EXPERIMENTAL MEDICINE
影响因子：
15.3
作者：
Marusic, S;Leach, MW;Pelker, JW;Azoitei, ML;Uozumi, N;Cui, JQ;Shen, MWH;DeClercq, CM;Miyashiro, JS;Carito, BA;Thakker, P;Simmons, DL;Leonard, JP;Shimizu, T;Clark, JD
通讯作者：
Clark, JD

Identification of the lntracellular region of the Leukotriene B4 receptor type-1 tnat specifically involves in Gi-activation.

1 型白三烯 B4 受体 tnat 细胞内区域的鉴定特别涉及 Gi 激活。

DOI：
发表时间：
2007
期刊：
J. Biol. Chem. 282
影响因子：
0
作者：
Kuniyeda;K.;Okuno;T.;Terawaki;K.;Miyano;M.;Yokomizo;T.;Shimizu;T.
通讯作者：
T.

Cytosolic Phospholipase A2 ・ deficient Mice Are Resistant to Collagen-induced Arthritis

胞质磷脂酶 A2·缺陷小鼠对胶原蛋白诱导的关节炎有抵抗力

DOI：
发表时间：
2003
期刊：
J. Exp. Med. 197
影响因子：
0
作者：
Hegen;M.;Sun L.;Uozumi N.;Kume K.;Goad;E. M.;Nickerson-Nutter L. C.;Shimizu T.;Clark D. J.
通讯作者：
Clark D. J.

Lipid mediators ; fundamental regulators of immune responses and inflammatory reactions.

脂质介质；