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Study on the tissue specific expression of phosphatidylinositol synthase and its function.

磷脂酰肌醇合酶的组织特异性表达及其功能研究。

基本信息

批准号：
09680612
负责人：
HOSAKA Kohei
金额：
$ 2.18万
依托单位：
Gunma University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09680612/
关键词：
in situ hybridization mRNA phosphatidylinositol synthase distribution in brain cell cycle inhibitor cyclinD cyclinE ラットホスファチジルイノシトールホスファチジルイノシトール合成酵素 G1期サイクリンD サイクリンE リン脂質インサイトハイブリダゼイーション mRNA 海馬

项目摘要

Phosphatidylinositol synthase (PIS) catalyzes the formation of phosphatidylinositol (Pl) from myo-inositol and CDP-diacylglyceol and mediates the final step in the biosynthetic sequence leading to phosphoinositide. We have recently isolated and characterized a PIS cDNA from rat brain. The results obtained by this project are follows :i) In situ hybridization histochemistry revealed that PIS mRNA is selectively expressed in neuron-rich regions of the adult rat brain, such as cerebral cortex, hippocampus, thalamus, hypothalamus, and spinal cord. By contrast, little to no hybridization signal was observed in white matter-rich areas such as the corpus callosum. The expression of PIS mRNA was determinated during pre- and postnatal development of the rat central nervous system. On embryonic day 18, PIS was expressed mainly neuron-enriched areas such as cortical plate and ventricular zone whereas little to no mRNA is detected in glia-enriched areas.ii) Quantitative reverse transcription-polymerase chain reaction analysis as well as in situ hybridization showed that the PIS transcript level dramatically increased during the first postnatal week, and peaked at 7-14 days after birth.iii) Since the preliminary results suggested the presence of a new isoform of PIS, I tried to clone the isoform with several methods. But the new clone could not be isolated.iv) Dr. Umezawa(Keio Univ.) reported that inostamycin, known as a specific inhibitor of Pl synthesis, blocked both the Pl synthesis and G1 progression in the serum stimulated rat fibroblast cells. The collaboration study with him revealed that another inhibitor, delta- hexachlorocyclohexane, also blocked the both activity as inostamycin. Furthermore the blockade was due to the inhibition of the expression cyclin D and cyclin E.These results suggest that P13 plays an important role in cell cycle.

磷脂酰肌醇合酶（PIS）催化肌醇和CDP-二酰基甘油形成磷脂酰肌醇（PI），并介导生物合成序列中导致磷酸肌醇的最后一步。我们最近从大鼠脑中分离并鉴定了PIS cDNA。本课题获得的结果如下：（1）原位杂交组织化学显示，PIS mRNA选择性地表达于成年大鼠脑内神经元丰富的区域，如大脑皮质、海马、丘脑、下丘脑和脊髓。相比之下，在白色物质丰富的区域如胼胝体中几乎没有观察到杂交信号。本研究测定了PIS mRNA在大鼠中枢神经系统发育过程中的表达。在胚胎第18天，PIS主要表达于神经元富集的区域，如皮质板和脑室区，而在胶质细胞富集的区域检测到很少或没有mRNA。ii）定量逆转录-聚合酶链反应分析以及原位杂交显示，PIS转录水平在出生后第一周显著增加，3）由于初步结果提示PIS存在一种新的异构体，我尝试用几种方法克隆该异构体。但是新的克隆体不能被分离出来。iv）梅泽博士（庆应义塾大学）报道称，被称为Pl合成特异性抑制剂的伊诺霉素可以阻断血清刺激的大鼠成纤维细胞中的Pl合成和G1期进展。与他的合作研究表明，另一种抑制剂，δ-六氯环己烷，也阻止了这两个活动作为inostamycin。P13对细胞周期的抑制作用可能与抑制cyclin D和cyclin E的表达有关，提示P13在细胞周期中起重要作用。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Hideshi Iwai他4名: "Differentcal distrbution of mRNA emoding phosphatidyl inasrtaltrancfor proteins α and β in the central nernois system of the rat" Mol.Brain Res.46. 256-264 (1997)

Hideshi Iwai 和其他 4 人：“大鼠中枢神经系统中表达磷脂酰胰岛素转运蛋白 α 和 β 的 mRNA 的不同分布”Mol.Brain Res.46 (1997)。

DOI：
发表时间：
期刊：
影响因子：
0
作者：
通讯作者：

S.kagiwada, K.Hosaka 他 3名: "The Saaharo myus cerevisiae SCS2 gene product, a homolog of a synatobrurn-associated protein, 25an integral mombnene prokm of fliendu bsmieritzwlum and is neguiie for inosufel 〓" J.Baeferiol.180. 1700-1708 (1998)

S.kagiwada、K.Hosaka 和其他 3 人：“Saaharo myus cerevisiae SCS2 基因产物，一种 synatobrurn 相关蛋白的同源物，fliendu bsmieritzwlum 的 25an 完整 mombnene prokm，并且是 inosufel 〓的 neguiie”J.Baeferiol.180。 -1708 (1998)