Effects of 2-hydroxyoleic acid on the structural properties of biological and model plasma membranes

Abstract

This article maybe used for research, teaching and private study purposes. Any substantial or systematic reproduction, re-distribution, re-selling, loan or sub-licensing, systematic supply or distribution in any form to anyone is expressly forbidden.The publisher does not give any warranty express or implied or make any representation that the contents will be complete or accurate or up to date. The accuracy of any instructions, formulae and drug doses should be independently verified with primary sources. The publisher shall not be liable for any loss, actions, claims, proceedings, demand or costs or damages whatsoever or howsoever caused arising directly or indirectly in connection with or arising out of the use of this material. AbstractGenetic hypertension is associated with alterations in lipid metabolism, membrane lipid composition and membraneprotein 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 H II -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 Gaq/11 protein and hence, signal transduction.

Interactions of fatty acids with phosphatidylethanolamine membranes: X-ray diffraction and molecular dynamics studies

“…In turn, 2OHOA showed a highly increased antihypertensive action in genetically hypertensive rats ( 18 ). Moreover, reconstituted plasma membranes from these rats showed a clear shift of their biophysical properties toward a higher propensity to form H II phases, paralleled by a signifi cant increase in the level of unsaturated FAs ( 16 ). Although these results do not fi rmly establish the molecular mechanism of action of 2OHOA, they indicate that the observed alteration of biophysical membrane parameters in vitro also occurs in vivo and should have pharmacological relevance.…”

“…2-Hydroxyoleic acid (2OHOA), a synthetic derivative of the naturally occurring oleic acid, induced the formation of H II structures in model membranes ( 15 ). In vivo, this observation was paralleled by an alteration of the membrane lipid composition which was related to the observed increase of G proteins in the plasma membrane of 2OHOA-treated animals ( 12,16 ). Moreover, 2OHOA showed a strongly enhanced antihypertensive action in this animal model of hypertension ( 17,18 ), thus demonstrating the viability of this new pharmacological approach.…”

Mediterranean-Style Diet Effect on the Structural Properties of the Erythrocyte Cell Membrane of Hypertensive Patients

“…17 Multilamellar lipid vesicles, 15% (wt/wt) with total lipid extracts, were prepared in 10 mmol/L of HEPES, 100 mmol/L of NaCl, and 1 mmol/L of EDTA (pH 7.4; HEPES buffer). 12 Lipid mixtures were hydrated, thoroughly homogenized with a pestle-type minihomogenizer (Sigma), and vortexed until a homogeneous mixture was obtained. Then, the suspensions were submitted to 5 temperature cycles (heated up to 70°C and cooled down to 4°C).…”

“…8 -10 Changes in membrane lipid composition of hypertensive subjects have been associated with alterations in the transmembrane fluxes of Na ϩ and K ϩ , including Na ϩ -Li ϩ countertransport, which is a marker of essential hypertension, 10,11 and in cell signaling proteins that participate in the control of blood pressure. 12 On the other hand, it has been reported that dietary lipids have an effect on membrane lipid composition and cell signaling proteins. 4,5,12 Considering that changes in the dietary lipid composition yield to variations in the biophysical properties of the plasma membrane, it is likely that cellular functional changes could result from alterations in the structure of the lipid membrane properties influenced by the diet.…”

“…12 On the other hand, it has been reported that dietary lipids have an effect on membrane lipid composition and cell signaling proteins. 4,5,12 Considering that changes in the dietary lipid composition yield to variations in the biophysical properties of the plasma membrane, it is likely that cellular functional changes could result from alterations in the structure of the lipid membrane properties influenced by the diet. Thus, the changes in membrane properties induced by dietary lipids may have important consequences on blood pressure regulation.…”