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PI-response and Signal Tranadut in Myocardial Gamage

心肌细胞中的 PI 反应和信号 Tranadut

基本信息

批准号：
63480220
负责人：
KAWAGUCHI Hideaki
金额：
$ 3.2万
依托单位：
Hokkaido University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1988
资助国家：
日本
起止时间：
1988 至 1989
项目状态：
已结题

项目摘要

The primary event in the mechanism of action of many different hormones and neurotransmitters involves receptor-mediated stimulation of the breakdown of plasma membrane inositol phospholipids. This so-called phosphatidylinositol (PI) turnover pathway generates two second messengers, inositol- (1, 4,5) trisphosphate (IP_3) and sn 1, 2-diacyglycerol (DAG). DAG stimulates membrane-bound phospho-lipid-dependent, Ca^<2+>-dependent protein kinase C while IP_3, releases Ca^<2+> from endoplasmic reticulum stores. We consider that Plーturnover pathway has a quite important role in inducing cardiac myocyte hypertrophy. The purpose of this experiment is to study the properties of inositoltrisphostate kinase in hypertrophied rat heart.In the present experiment, we demonstrated that inositol- (1, 4, 5) tris-phosphate (IP_3) kinase activity was increased in the stroke-prone spontaneously hypertensive rat (SHRSP) heart compared to the Wistar Kyoto rat (WKY). IP_3 kinase activity in the heart was highest in the cytosolic fraction in both SHRSP and WKY. Its activity progressively increased with age in SHRSP aged 5 to 20 weeks. The activity reached about three times the level of 5-week-old SHRSP in 40-weeks-old SHRSP. On the other hand, in WKY it was 1.3-fold at 40 weeks compared with 5-week-olds. We determined the effect of divalent cations on IP_3 kinase activity. Ca^<2+> stimulated its activity in a dose-dependent manner at 10^<-9> to 10^<-6>M. In SHRSP it was enhanced about 2.1-fold at 10^<-6>M of Ca^<2+>, but in WKY it was 1.5-fold at 10^<-6>M of Ca^<2+>. Mn^<2+> also stimulated IP_3 kinase activity in both groups of animals, while, Fe^<2+>, Zn^<2+>, and Cu^<2+> inhibited IP_3 kinase activity. In our experiment IP_3 kinase activity was increased in SHRSP and its activity was markedly affected by divalent cations. These data suggest the accumulations of IP_3 and IP_4 after hormonal stimulation have a physiologic role, possibly by alteration of Ca^<2+> levels in cardiac tissue.

许多不同激素和神经递质作用机制中的主要事件涉及受体介导的质膜肌醇磷脂分解的刺激。这种所谓的磷脂酰肌醇 (PI) 周转途径会产生两个第二信使：肌醇-(1, 4,5) 三磷酸 (IP_3) 和 sn 1, 2-二酰甘油 (DAG)。 DAG刺激膜结合的磷脂依赖性、Ca 2+ 依赖性蛋白激酶C，而IP_3从内质网储存中释放Ca 2+ 。我们认为Plー周转途径在诱导心肌细胞肥大中具有相当重要的作用。本实验的目的是研究肌醇三磷酸激酶在肥大大鼠心脏中的特性。在本实验中，我们证明与 Wistar 京都大鼠 (WKY) 相比，肌醇-(1,4,5)三磷酸 (IP_3) 激酶活性在易发生中风的自发性高血压大鼠 (SHRSP) 心脏中增加。在 SHRSP 和 WKY 中，心脏中的 IP_3 激酶活性在胞质部分中最高。在 5 至 20 周的 SHRSP 中，其活性随着年龄的增长而逐渐增加。 40周龄SHRSP的活性达到5周龄SHRSP水平的约三倍。另一方面，在 WKY 中，40 周龄时的比率是 5 周龄时的 1.3 倍。我们确定了二价阳离子对 IP_3 激酶活性的影响。 Ca 2+ 在10 ^ -9 至10 ^ -6 M以剂量依赖性方式刺激其活性。在SHRSP中，在Ca ^ 2+ 为10 ^ -6 M时，其增强约2.1倍，但在WKY中，在Ca ^ 2+ 为10 ^ -6 M时，其增强约1.5倍。 Mn ^ 2+ 还刺激两组动物中的IP_3激酶活性，而Fe ^ 2+ 、Zn ^ 2+ 和Cu ^ 2+ 抑制IP_3激酶活性。在我们的实验中，SHRSP 中 IP_3 激酶活性增加，并且其活性明显受到二价阳离子的影响。这些数据表明激素刺激后IP_3和IP_4的积累具有生理作用，可能通过改变心脏组织中的Ca 2+ 水平来实现。