Role of phosphatidylethanol in membranes. Effects on membrane fluidity, tolerance to ethanol, and activity of membrane-bound enzymes

Abstract

We investigated the effect of phosphatidylethanol (PEt) on fluidity and membrane tolerance to the fluidization induced by ethanol as well as on the activity of two membrane-bound enzymes, Na+/K+ ATPase and 5'-nucleotidase. PEt was synthesized from 1,2-dimyristoylphosphatidylcholine and phosphatidylcholine from bovine brain and studies were performed to determine the optimal experimental conditions for the insertion of PEt in natural bilayers. The effects of PEt, evaluated by differential scanning calorimetry or fluorescence polarization techniques, were studied in model membranes made of synthetic phospholipids or made of total lipids extracted from rat brain crude mitochondrial fraction (P2 fraction) and from natural membranes (P2 fraction). The presence of PEt increased the fluidity of artificial as well of natural membranes, but tolerance to the addition of ethanol, displayed by dimyristoylphosphatidylcholine vesicles and by natural membranes containing PEt, was lacking in vesicles made of dimyristoylphosphatidylethanolamine and in artificial bilayers reconstituted from total P2 lipid extracts, suggesting an involvement of PC on PEt-induced ethanol resistance. Na+/K+ ATPase activity was enhanced by the addition of small amounts of ethanol (up to 50 mM) and progressively inhibited at higher concentrations, while 5'-nucleotidase was not affected up to 400 mM ethanol. The presence of PEt in the bilayer exerted the opposite effects on the two enzymes, reducing the Na+/K+ ATPase activation induced by ethanol and enhancing 5'-nucleotidase activity. The mechanisms of the PEt-induced modifications are discussed.

Phosphatidylethanol Accumulation Promotes Intestinal Hyperplasia by Inducing ZONAB-Mediated Cell Density Increase in Response to Chronic Ethanol Exposure

“…Another important finding of our study was the demonstration that the resulting loss of association between ZO-1 and ZONAB was due to the accumulation of phosphatidylethanol in the membrane of ethanol-treated cells, which may induce a disruption of the local phospholipid environment, as previously reported (41). The production of phosphatidylethanol, mediated by ethanol-induced PLD activation, was shown for the first time to be essential for the increase of proliferation and maximal cell density in Caco-2/TC7 cells.…”

Membrane lipid physiology and toxin catabolism underlie ethanol and acetic acid tolerance inDrosophila melanogaster

“…Ethanol effectively competes with water as a substrate for PLD, resulting in the accumulation of phosphatidylethanol (PEth) at the expense of the normal signaling molecule, 1,2-DAG ( Fig.·1) (Gustavsson, 1995). PEth increases membrane fluidity, but the presence of PEth in membrane lipid bilayers may also confer some tolerance to ethanol-induced membrane disruption (Omodeo-Sale et al, 1991). In our experiments, Pld expression and PLD activity were increased in the more ethanol tolerant warm-acclimated and thermally down-shifted flies.…”

Peroxisomal Proliferation in Rat Liver and Essential Fatty Acid Deficiency

“…Besides, in CC group the membrane is in evidence altered to be more fluid as experimentally confirmed [33]. However, fine tuning in the interaction between lipid membrane and enzyme proteins was probably regulated by double bond position of UFAs and by polarity of PL head groups [24,25,31]. This would in part explain additionally to variation in membrane fluidity, how DHAP-AT and palmitoyl-CoA synthetase activities were differentially affected by the various diets.…”

“…The low rate of PI incorporation into peroxisomal membrane in CC group might be the reflect of a preferential incorporation of endogeneous polyUFAs into PE and Sph that had a slight percentage increase and also into PC. Indispensable role of these PLs is emphasized by their properties in regulating membrane fluidity and interaction of protein with polar head group of the PLs [24,25]. It was also suggested that PI-dependent transduction signal could be induced by CLO [26], thus possibly affecting the PI turnover and its incorporation into peroxisomal membrane.…”