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Origin and Disappearance of Diacylglycerol, a Protein Kinase C Activator, in Salivary Glands

唾液腺中蛋白激酶 C 激活剂二酰甘油的起源和消失

基本信息

批准号：
01571034
负责人：
YOKOTA Yutaka
金额：
$ 1.28万
依托单位：
Asahi University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1989
资助国家：
日本
起止时间：
1989 至 1990
项目状态：
已结题

项目摘要

Membrane lipids play an important role in signal transmission via their specific metabolic pathways. Especially, there are many reports that newly formed diacylglycerol (DAG) through receptor activation binds to protein kinase C resulting in enhancement of its Ca^<2+>-sensitivity. Therefore, DAG attracts many attentions as an activator of protein kinase C in many cellular systems including secretory one. In this study, we have characterized the acyl chain composition of DAG and the related metabolic pathway to approach the clarification of origin and disappearance of DAG in secretory cells.The acyl chain of DAG from both homogenate of rat submandibular and sublingual salivary glands mainly consisted of saturated fatty acids (more than 79% of the total) such as palmitic and stearic acids. Although oleic acid existed 13% of the total, polyunsaturated ones were very little in DAG. This profile of saturated fatty acid enrichment was similar to the acyl chain composition of triacylglycerol … More rather than those of phosphatidylcholine and phosphatidylethanolamine although 1-stearoyl-2-arachidonoyl-DAG was known as a potent activator of protein kinase C. Therefore, the feature of DAG formed in signal transmission was thought to result from conversion from phospholipid to DAG or deacylation-reacylation during cell activation. Concerning the deacylation-reacylation pathway, we clarified the substrate specificities of microsomal phospholipase A_2, 1-acylglycerophosphate acyltransferase and 1-acylglycerophosphocholine acyltransferase. Furthermore, composition of ether-linked phospholipids and their side chain composition were established comparing properties of 1-alkenylglycerophosphocholine acyltransferase. On the other hand, membrane-bound phospholipase A_2 having different substrate specificity from the microsomal one was detected in secretory granules ; functional relationship between the requirement of granular membrane lipids and membrane fusion was also suggested.These results are thought to contribute the clarification of lipid metabolism responding to secretory stimulus in the cells. Less

膜脂通过其特定的代谢途径在信号传递中起重要作用。特别是，有许多报道新形成的甘油二酯（diacylglycerol，DAG）通过受体活化与蛋白激酶C结合，导致其Ca^2+敏感性增强。因此，达格作为许多细胞系统（包括分泌系统）中蛋白激酶C的激活剂而引起了人们的广泛关注。本文通过对大鼠颌下腺和舌下腺唾液腺匀浆中DAG的酰基链组成及代谢途径的研究，发现大鼠颌下腺和舌下腺唾液腺匀浆中DAG的酰基链主要由饱和脂肪酸（79%以上）组成，如棕榈酸和硬脂酸。油酸占总油酸的13%，而多不饱和脂肪酸含量很少。这种饱和脂肪酸富集的概况与三酰甘油的酰基链组成相似 ...更多信息而不是磷脂酰胆碱和磷脂酰乙醇胺的那些，尽管已知1-硬脂酰-2-花生四烯酸酰-DAG是蛋白激酶C的有效激活剂。因此，在信号传递中形成的DAG的特征被认为是在细胞活化过程中从磷脂转化为DAG或脱酰-再酰化的结果。关于脱酰-再酰化途径，我们阐明了微粒体磷脂酶A_2、1-酰基甘油磷酸酰基转移酶和1-酰基甘油磷酸胆碱酰基转移酶的底物特异性。此外，醚连接的磷脂和它们的侧链组成的组成建立比较1-烯基甘油磷酸胆碱酰基转移酶的性质。另一方面，在分泌颗粒中检测到与微粒体磷脂酶不同的底物特异性膜结合磷脂酶A_2，并提出了颗粒膜脂的需求与膜融合之间的功能关系，这些结果有助于阐明细胞内对分泌刺激的脂质代谢反应。少