Polyunsaturated fatty acids and signalling via phospholipase C-beta and A(2) in myocardium
Polyunsaturated fatty acids and signalling via phospholipase C-beta and A(2) in myocardium
复制标题
DOI：
10.1007/bf00227899
复制
发表时间：
1996-04-12
影响因子：
4.3
通讯作者：
Lamers, JMJ
中科院分区：
文献类型：
--
作者：
deJonge, HW;Dekkers, DHW;Lamers, JMJ
膳食n-6和n-3多不饱和脂肪酸（PUFA）对血液（细胞）、血管系统和心肌具有潜在的生物学效应。在流行病学研究中，报告了定期摄入n-3多不饱和脂肪酸的益处，但相关机制仍不清楚。大量的PUFA效应可以通过已知的对类花生酸代谢的干扰来解释。许多被认为参与动脉粥样硬化形成的过程，如血细胞粘附和浸润到血管系统、血小板聚集、内皮衍生因子的分泌和血管平滑肌细胞的促有丝分裂反应，部分由受体激活的磷脂酶C-β和A介导（2）。由于PUFA参与信号通路的许多步骤，后者可能代表重要的作用位点，以有益地干扰动脉粥样硬化形成。在这篇简短的综述中，我们讨论了改变膜磷脂的PUFA组合物或外源性非酯化PUFA对磷脂信号传导的影响的研究结果。为方便起见，我们主要集中讨论心肌方面的研究。通过改变磷脂的PUFA组成，改变了膜相关磷脂酶C-β和A（2）的内源性底物。这伴随着它们对这些底物的水解作用的变化，导致产物改变（1，2-二酰基甘油和非酯化PUFA的分子种类），这反过来又引起信号级联下游事件的变化：激活不同的蛋白激酶C同工酶，形成不同的类花生酸和非酯化PUFA对Ca 2+通道的影响。它也变得更加清楚，膜的物理化学性质，在流动性和胆固醇含量的双层，可能会发生变化，由于改变PUFA纳入膜磷脂。后一种效应可能对受体功能、受体-GTP结合蛋白偶联、GTP结合蛋白-磷脂酶C-β或A（2）偶联产生影响。应该注意的是，这些研究中的大多数是用从PUFA饮食动物心脏分离的心肌细胞或在白蛋白存在下用非酯化PUFA孵育培养的心肌细胞进行的。需要进行研究以证明PUFA饮食诱导的磷脂信号传导反应的调节确实在体内发生，并且这些作用涉及饮食PUFA对动脉粥样硬化过程的有益作用的机制。
Dietary n-6 and n-3 polyunsaturated fatty acids (PUFAs) have potent biological effects on the blood(cells), the vasculature and the myocardium. In the epidemiological studies in which the benefit from the regular ingestion of n-3 PUFAs was reported, the responsible mechanisms remain obscure. A great deal of the PUFA-effect can be explained by the known interference with the eicosanoid metabolism. Many processes, believed to be involved in atherogenesis such as adhesion and infiltration of bloodcells (in)to the vasculature, platelet aggregation, secretion of endothelium-derived factors and mitogenic responses of vascular smooth muscle cells are partially mediated by receptor-activated phospholipases C-beta and A(2). As PUFAs take part at many steps of the signalling pathways, the latter could represent important action sites to beneficially interfere with atherogenesis. In this brief review, we have discussed the results of studies on the influence of alteration of PUFA composition of the membrane phospholipids or of exogenously administered non-esterified PUFAs on phospholipid signalling. For convenience, we have mainly focused our discussion on those studies available on the myocardium. By changing the PUFA composition of the phospholipids, the endogenous substrates for the membrane-associated phospholipase C-beta and A(2) are changed. This is accompanied by changes in their hydrolytic action on these substrates resulting in altered products (the molecular species of 1,2-diacylglycerols and the non-esterified PUFAs) which on their turn evoke changes in events downstream of the signalling cascades: activation of distinct protein kinase C isoenzymes, formation of distinct eicosanoids and non-esterified PUFA effects on Ca2+ channels. It has also become more clear that the membrane physicochemical properties, in terms of fluidity and cholesterol content of the bilayer, might undergo changes due to altered PUFA incorporation into the membrane phospholipids. The latter effects could have consequences for the receptor functioning, receptor-GTP-binding protein coupling, GTP-binding protein-phospholipase C-beta or A(2) coupling as well. It should be noted that most of these studies have been carried out with cardiomyocytes isolated from hearts of animals on PUFA diet or incubation of cultured cardiomyocytes with non-esterified PUFAs in the presence of albumin. Studies need to be performed to prove that the PUFA-diet induced modulations of the phospholipid signalling reactions do occur in vivo and that these effects are involved in the mechanism of beneficial effects of dietary PUFAs on the process of atherosclerosis.