Abstract
N-3 eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) seem to prevent endothelial dysfunction, a crucial step in atherogenesis, by modulating the levels of vasoactive molecules and by influencing Na,K-ATPase activity of vascular myocytes. The activity of endothelial Na,K-ATPase controls the ionic homeostasis of the neighboring cells, as well as cell function. However, controversy exists with respect to the vascular protective effect of EPA and DHA. We argue that this dispute might be due to the use of different concentrations of EPA and DHA in different studies. Therefore, this study was designed to define an optimal concentration of EPA and DHA to investigate endothelial function. For this purpose, human endothelial cells were exposed for 24 h to different concentrations of DHA or EPA (0–20 μM) to study membrane fluidity, peroxidation potential and Na,K-ATPase activity. EPA and DHA were linearly incorporated and this incorporation was mirrored by the linear increase of unsaturation index, membrane fluidity, and peroxidation potential. Na,K-ATPase activity peaked at 3.75 μM of EPA and DHA and then gradually decreased. It is noteworthy that DHA effects were always more pronounced than EPA. Concluding, low concentrations of EPA and DHA minimize peroxidation sensitivity and optimize Na,K-ATPase activity.
Highlights
IntroductionThe Na,K-ATPase or Na+ pump (EC 3.6.37) is an ubiquitous membrane transport protein whose activity determines and maintains high K+ and low Na+ concentrations in the cytoplasm, generates a potential across the membrane and provides the driving force for secondary ion transport [1]
The Na,K-ATPase or Na+ pump (EC 3.6.37) is an ubiquitous membrane transport protein whose activity determines and maintains high K+ and low Na+ concentrations in the cytoplasm, generates a potential across the membrane and provides the driving force for secondary ion transport [1].Na,K-ATPase consists of two subunits: A large ouabain-sensitive polypeptide (α) responsible for transporting ions and a smaller glycoprotein (β) needed for enzymatic activity
Several human studies suggest that high levels of the n-3 long-chain (LC) polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid and docosahexaenoic acid in membrane phospholipids reduce cardiovascular risk [12,13] and improve endothelial function [14]
Summary
The Na,K-ATPase or Na+ pump (EC 3.6.37) is an ubiquitous membrane transport protein whose activity determines and maintains high K+ and low Na+ concentrations in the cytoplasm, generates a potential across the membrane and provides the driving force for secondary ion transport [1]. Several human studies suggest that high levels of the n-3 long-chain (LC) polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid and docosahexaenoic acid in membrane phospholipids reduce cardiovascular risk [12,13] and improve endothelial function [14]. It is widely believed that lipids that increase membrane fluidity promote Na,K-ATPase activation, and, vice versa, those that stiffen the membranes reduce pump activity [20] Membrane lipids, such as phospholipid species, their fatty acyl chain length and degree of unsaturation, and cholesterol content all contribute to the fluidity of the membranes. 33 of of 12 present study to investigate the effects of different concentrations of EPA or DHA on Na,K-ATPase activity and and membrane membranechemical-physical chemical-physicalparameters parameters that could affect activity of ATPase, this ATPase, that could affect the the activity of this such such the degree of membrane fluidity and the susceptibility to lipid peroxidation in human as theas degree of membrane fluidity and the susceptibility to lipid peroxidation in human microvascular microvascular endothelial endothelial cells (HMEC). cells (HMEC)
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