Prades Jesús, Alemany Regina, Perona Javier S, Funari Sérgio S, Vögler Oliver, Ruiz-Gutiérrez Valentina, Escribá Pablo V, Barceló Francisca
Molecular and Cellular Biomedicine, Health Sciences Research Institute, University of the Balearic Islands, Palma de Mallorca, Spain.
Mol Membr Biol. 2008 Jan;25(1):46-57. doi: 10.1080/09687680701510042.
Genetic hypertension is associated with alterations in lipid metabolism, membrane lipid composition and membrane-protein function. 2-Hydroxyoleic acid (2OHOA) is a new antihypertensive molecule that regulates the structure of model membranes and their interaction with certain peripheral signalling proteins in vitro. While the effect of 2OHOA on elevated blood pressure is thought to arise through its influence on signalling proteins, its effects on membrane lipid composition remain to be assessed. 2OHOA administration altered the lipid membrane composition of hypertensive and normotensive rat plasma membranes, and increased the fluidity of reconstituted liver membranes from hypertensive rats. In spontaneously hypertensive rats (SHR), treatment with 2OHOA increased the cholesterol and sphingomyelin content while decreasing that of phosphatidylserine-phosphatidylinositol lipids. In addition, monounsaturated fatty acid levels increased as well as the propensity of reconstituted membranes to form HII-phases. These data suggest that 2OHOA regulates lipid metabolism that is altered in hypertensive animals, and that it affects the structural properties of liver plasma membranes in SHR. These changes in the structural properties of the plasma membrane may modulate the activity of signalling proteins that associate with the cell membrane such as the Galphaq/11 protein and hence, signal transduction.
遗传性高血压与脂质代谢、膜脂质组成和膜蛋白功能的改变有关。2-羟基油酸(2OHOA)是一种新型抗高血压分子,在体外可调节模型膜的结构及其与某些外周信号蛋白的相互作用。虽然认为2OHOA对血压升高的影响是通过其对信号蛋白的作用产生的,但其对膜脂质组成的影响仍有待评估。给予2OHOA可改变高血压和正常血压大鼠质膜的脂质膜组成,并增加高血压大鼠重构肝细胞膜的流动性。在自发性高血压大鼠(SHR)中,用2OHOA治疗可增加胆固醇和鞘磷脂含量,同时降低磷脂酰丝氨酸-磷脂酰肌醇脂质的含量。此外,单不饱和脂肪酸水平增加,重构膜形成HII相的倾向也增加。这些数据表明,2OHOA调节高血压动物中发生改变的脂质代谢,并影响SHR肝质膜的结构特性。质膜结构特性的这些变化可能会调节与细胞膜相关的信号蛋白(如Galphaq/11蛋白)的活性,从而影响信号转导。