Ethanol-induced modifications to membrane lipid structure: Effect on phospholipase A2-membrane interactions (original) (raw)
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Biochimica et Biophysica Acta (BBA) - Biomembranes, 1991
Chronic ethanol ingestion leads to the acquisition of a tolerance to membrane lipid disordering, a lowered partition coefficient to hydrophobic compounds and a resistance to the hydrolysis of the phospholipids by exogenous phospholipase A 2. Anionic phospholipids have been implicated as being responsible for the resistance to lipid disordering and a number of modifications to these phospholipids are known to occur as a result of chronic ethanol-ingestion. In this study the basis of the resistance to phospholipase A 2 in hepatic microsomes was investigated. It was found that chronic ethanol-induced moditications to each of the major phospholipid classes was responsible to some extent for the resistance to phospholipase A 2, however, PS was particularly potent considering it is a compositionally minor constituent. The effect was interpreted as a reduced ability to activate the phospholipase A z since PS acts as an essential activator of phospholipase A 2 (along with PI). Fatty acid analysis revealed that the chronic ethanol-treatment resulted in a elevated level of docosahexaenoate with a parallel reduction in arachidonate in phosphatidylserine. Lipid packing and organization is important in the regulating the level of exogenous phospholipase A 2 activity but the activity was not found to correlate with lipid order of different phosphatidylserine species. It is concluded that subtle differences in the molecular species arrangement or disposition around the enzyme may be responsible for the altered phospholipase A 2 interaction with the membrane induced by chronic ethanol-treatment. One implication of this study is that other anionic phospholipid dependent membrane proteins, of which there are many known examples, may also be modified as a result of chronic ethanol-ingestion.
Proceedings of the National Academy of Sciences, 1986
The structural properties of liver microsomes and erythrocytes obtained from rats that had been chronically administered ethanol were examined by electron spin resonance (ESR) following ethanol withdrawal for 1-10 days. Membranes obtained from control animals exhibited considerable molecular disordering upon the addition of ethanol in vitro (50-100 mM). Conversely, microsomal and erythrocyte membranes from alcoholic animals were resistant to this disordering by ethanol (membrane tolerance). These membrane properties were also apparent in lipid bilayers comprised of either total lipids or phospholipids isolated from the control and alcoholic animals. While several weeks of ethanol administration were required for both erythrocytes and microsomes to develop membrane tolerance, erythrocytes from alcoholic animals were disordered by ethanol in vitro after the animals had been withdrawn from ethanol for only 1 day. The same rapid loss of tolerance was observed in microsomes after 2 days of withdrawal. The same time course for the loss of tolerance was observed in lipid bilayers prepared from the total lipid and phospholipid extracts. No significant differences in the
Effects of chronic ethanol administration on the composition of membrane lipids in the mouse
Biochemical Pharmacology, 1982
The relative proportions of the phospholipid fatty acids of erythrocyte membranes in mice were changed by chronic ethanol treatment and were not related to effects of the drug on nutrition, body temperature or experimental stress. Similar changes were observed using two different routes of ethanol administration and they did not reflect the metabolic effects of ethanol seen in the phospholipid fatty acids of whole liver. The observed increased content of saturated fatty acids and decreased content of polyunsaturated acids support the concept of adaptive changes taking place in the membrane during tolerance development to compensate for an increased membrane fluidity caused by ethanol. However, an increased content of the mono-unsaturated acid, octadecenoic (oleic), was found and there was no change in the cholesterol/phospholipid ratio. Other contrasting types of plasma membrane in mice showed different patterns of change in their phospholipid fatty acids during chronic ethanol administration. It is suggested that changes in membrane lipid composition could only partly account for an adaptation to ethanol-induced membrane disordering.
Ethanol and biological membranes: Injury and adaptation
Pharmacology Biochemistry and Behavior, 1983
biological membranes: lnjuo ' and adaptation. PHARMACOL BIOCHEM BEHAV 18: Suppl. 1, 7-13, 1983.--Ethanol intoxication affects the protein and lipid constituents of biological membranes, Mitochondria exhibit specific decreases in components of the electron transport chain and in protein synthesis. In vitro ethanol reduces the transition temperatures of membrane-bound enzyme activities and decreases the order parameter. On the other hand, both are increased after chronic ethanol administration. After chronic ethanol treatment membranes are resistant to disordering by ethanol, possibly owing to an increased saturation of mitochondrial phospholipids, particularly cardiolipin. The increased rigidity of mitochondrial and synaptosomal membranes is associated with reduced binding of ethanol and of the general anesthetic halothane. The data suggest that initially ethanol increases the fluidity of all biological membranes. If continued chronically, this effect is balanced by a change in the lipid composition of the membranes, which increases their rigidity and makes them resistant to disordering by ethanol (homeoviscous adaptation). The change in molecular order reduces the binding of ethanol and other compounds, but also impairs a variety of membrane-bound functions. These changes may play a role in tolerance to ethanol and cross-tolerance to anesthetics, and in the pathogenesis of maladies associated with alcohol abuse.
Life Sciences, 2006
By experimenting with the aminoalcohols [3-3 H]serine and [2-14 C]ethanolamine we have been able to relate the effects of ethanol upon the biosynthesis of radioactive aminophospholipids (APL) in rat-liver microsomes and their distribution within the bilayer. The translocation of newly synthesized molecules of aminophospholipids labeled with different fatty acids was also investigated. The synthesis of phosphatidylserine (PS) and phosphatidylethanolamine (PE) by base-exchange reaction (BES) was inhibited in membranes exposed to ethanol in direct response to its concentration. In addition, 100 mM ethanol specifically inhibited the transport of newly synthesized PS to the inner leaflet, resulting in similar levels of PS in both leaflets of the bilayer. The inhibition of PE synthesis by ethanol caused a decrease in its distribution in both inner and outer leaflets. An in vitro study of the incorporation of radioactive palmitate and oleate into the PS and PE of microsomes incubated with ethanol showed a decrease in the radioactivity levels of PE, suggesting that ethanol was specifically inhibiting the corresponding acyltransferase. It specifically altered the transbilayer movement of newly acylated phospholipids, modifying the distribution of palmitoyl-and oleoyl-acylated PS and PE in both leaflets. These results demonstrate for the first time that ethanol interferes with both the synthesis and intramembrane transport of aminophospholipids in endoplasmic reticulum (ER) membranes. Bearing in mind that if a membrane is to function properly its structure must be in optimum condition; it is evident that the observed processes may be responsible to some degree for the pathophysiological effects of alcohol upon cells.
Alcohol, 1988
Effects of ethanol and calcium on lipid order of membranes from mice selected for genetic differences in ethanol intoxication. ALCOHOL 5(3) 251-257, 1988.~ Fluorescent probes were used to compare the physical properties of membranes from mice selected for sensitivity (LS) and insensitivity (SS) to the hypnotic action of ethanol. Brain synaptic plasma membranes (SPM) from LS mice were more sensitive to the disordering action of ethanol than those from LS mice when probes were located near the membrane surface. However, the membrane core of membranes from the two lines was equally sensitive to ethanol. The genetic differences in ethanol sensitivity of the membrane surface were eliminated when fluorescence measurements were carried out in the presence of 2-3 mM CaCI~. Consistent with behavioral data, differential genetic sensitivity to the disordering action was not obtained with longer chain alcohols. The genetic difference in ethanol sensitivity was not detected with erythrocyte membranes or lipids extracted from SPM. These results indicate that there is a structural difference in the surface of brain membranes of LS and SS mice than may influence their sensitivity to ethanol.
Phospholipase Activity Is Enhanced in Liver Microsomes from Chronic Alcoholic Rats
Annals of the New York Academy of Sciences, 1987
Chronic ethanol intake is known to give rise to a resistance in cell membranes to the disordering effect of the lipids, in-vitro addition of other hydrophobic agents as well as by ethanol itself (for reviews see REFS. 1, 2). Also alterations in the fatty acid profiles of the phospholipids have been demonstrated to occur. We have therefore initiated studies on the enzymes involved in the re-tailoring of the membrane phospholipid fatty acid profiles and here report on studies on phospholipase activities in rat liver microsomes.
Annals of the New York Academy of Sciences, 1991
Chronic ethanol ingestion is known to induce adaptive changes in lipid composition which are thought to be responsible for a resistance to the disordering of the lipids by ethanol itself as well as by other membrane perturbing agents (reviewed in ref. 1). The fluorescence decay rates of the membrane lipid fluorophore probes 1,6-diphenyl-1,3,5-hexatriene (DPH) and l-palmitoyl-2-[[2-[4-(6-phenyl-trans-1,3,5-hexatricnyl]phenyll-ethyl]-carbony l1-3-sn-PC (DPH-PC) were used in order to investigate the effect of chronic ethanol treatment on membrane lipid structure. These fluorophores are very sensitive to the micro-environment in membranes.