Prostaglandin E(2) couples through EP(4) prostanoid receptors to induce IL-8 production in human colonic epithelial cell lines.

BACKGROUND AND PURPOSE: Prostaglandin (PG) E(2) and interleukin (IL)-8 are simultaneously increased during the inflammation that characterizes numerous pathologies such as inflammatory bowel disease. IL-8 is a potent neutrophil chemo-attractant and activator, and can initiate and/or exacerbate tissue injury. PGE(2) signals principally through prostanoid receptors of the EP(2) and/or EP(4) subtypes to promote cAMP-dependent cellular functions. The aim of this study was to identify the role of the EP(2) and EP(4) receptor subtype(s) on two human colonic epithelial cell lines (Caco-2 and T84), in regulating PGE(2)-induced IL-8 production. EXPERIMENTAL APPROACH: To identify the causative receptor, we knocked-down and over-expressed EP(2) and EP(4) receptor subtypes in colonic epithelial cells and studied the effect of several selective EP(2)/EP(4) receptor agonists and antagonists. The inductions of IL-8 and EP receptor mRNA and protein expression were determined by real-time PCR and western blot analysis. The affinity of PGE(2) and Bmax values for the EP(2) and EP(4) receptor on colonic epithelial cells were determined by radioligand-binding assays with [(3)H]PGE(2). KEY RESULTS: PGE(2) had the highest affinity for the EP(4) receptor subtype and promoted a robust stimulation of cAMP-dependent IL-8 synthesis. This effect was mimicked by a selective EP(4) receptor agonist, ONO-AE1-329, and abolished by silencing the EP(4) receptor gene by using siRNA techniques, a selective EP(4) receptor antagonist (ONO-AE3-208) and a selective inhibitor (Rp-cAMP) of cAMP-dependent protein kinase. CONCLUSIONS AND IMPLICATIONS: These findings suggest that initiation and progression of colonic inflammation induced by IL-8 could be mediated, at least in part, by PGE(2) acting via the EP(4) receptor subtype.

Gender inequality in nutritional status among under five children in a village in Hooghly district, West Bengal.

A community based, cross-sectional study was conducted in the Mollasimla village of Hooghly district of West Bengal, to examine the differences in nutritional status of under-five males and females and to determine the different bio-social factors associated with such differences. It was found that 55.9%, 51.4% and 42.3% of the girls were underweight, stunted and wasted respectively compared to 46.6%, 40.5% and 35.3% of the boys and a significantly higher proportion of malnutrition was found to be present among female children of higher birth order and those belonging to families with lower per capita income compared to the males.

Prostaglandin E2 receptor distribution and function in the gastrointestinal tract.

Prostaglandin E2 (PGE2) is one of the most important biologically active prostanoids found throughout the gastrointestinal tract. Despite the fact that PGE2 regulates many physiological functions of the gut including mucosal protection, gastrointestinal secretion and motility, it is implicated in the pathophysiology of inflammatory bowel diseases (IBD) and colorectal neoplasia. The varied biological functions exerted by PGE2 are through the pharmacologically distinct, G-protein coupled plasma membrane receptors termed EP receptors. Disruptions of various prostanoid receptor genes have helped in unravelling the physiological functions of these receptors. To date, all four subtypes of EP receptors have been individually knocked out in mice and various phenotypes have been reported for each subtype. Similarly, in vitro and in vivo studies using EP receptor agonists and antagonists have helped in uncoupling the diverse functions of PGE2 signalling involving distinct EP receptors in the gut. In this review, we will summarize and conceptualize the salient features of EP receptor subtypes, their regional functions in the gut and how expressions of EP receptors are altered during disease states.

Insight to structural subsite recognition in plant thiol protease-inhibitor complexes : understanding the basis of differential inhibition and the role of water.

BACKGROUND: This work represents an extensive MD simulation / water-dynamics studies on a series of complexes of inhibitors (leupeptin, E-64, E-64-C, ZPACK) and plant cysteine proteases (actinidin, caricain, chymopapain, calotropin DI) of papain family to understand the various interactions, water binding mode, factors influencing it and the structural basis of differential inhibition. RESULTS: The tertiary structure of the enzyme-inhibitor complexes were built by visual interactive modeling and energy minimization followed by dynamic simulation of 120 ps in water environment. DASA study with and without the inhibitor revealed the potential subsite residues involved in inhibition. Though the interaction involving main chain atoms are similar, critical inspection of the complexes reveal significant differences in the side chain interactions in S2-P2 and S3-P3 pairs due to sequence differences in the equivalent positions of respective subsites leading to differential inhibition. CONCLUSION: The key finding of the study is a conserved site of a water molecule near oxyanion hole of the enzyme active site, which is found in all the modeled complexes and in most crystal structures of papain family either native or complexed. Conserved water molecules at the ligand binding sites of these homologous proteins suggest the structural importance of the water, which changes the conventional definition of chemical geometry of inhibitor binding domain, its shape and complimentarity. The water mediated recognition of inhibitor to enzyme subsites (Pn.H2O.Sn) of leupeptin acetyl oxygen to caricain, chymopapain and calotropinDI is an additional information and offer valuable insight to potent inhibitor design.

In vivo delivery of antisense oligonucleotides in pH-sensitive liposomes inhibits lipopolysaccharide-induced production of tumor necrosis factor-alpha in rats.

Kupffer cells play an important role in the pathogenesis of liver diseases. During endotoxemia and alcohol-induced liver disease, tissue injury is preceded by an excessive release of cytokines by these macrophages. Tumor necrosis factor-alpha (TNF-alpha) is one of the key cytokines associated with liver injury. Pre-exposure of animals to TNF-alpha antibodies has been shown to prevent macrophage-mediated liver injury in experimental animals. In this article, we describe a method to encapsulate in pH-sensitive liposomes and to deliver an antisense phosphorothioate oligonucleotide (TJU-2755) against TNF-alpha. We describe the efficacy of this formulation in inhibiting endotoxin-mediated production of TNF-alpha. The liposomes prepared were stable for over 4 weeks at pH 7.4, but readily released their contents when exposed to an acidic environment below pH 6, similar to the pH that exists in early endosomes. Male Sprague-Dawley rats were administered (i.v.) liposome-encapsulated TJU-2755 (1-2 mg/kg body wt.). Empty liposomes served as controls. Forty-eight hours postinjection, the animals were administered a single dose of lipopolysaccharide (50 microg/kg body wt.) and were sacrificed 90 min later. The TNF-alpha produced by excised liver incubated ex vivo and the levels of plasma TNF-alpha were determined. After a single administration of liposome-encapsulated antisense TJU-2755, a 30% reduction in TNF-alpha produced by liver slices was observed. Two daily doses of the antisense oligonucleotide inhibited TNF-alpha production by 50%. This was associated with a 65 to 70% reduction in plasma levels of TNF-alpha, compared with controls. These results indicate that oligonucleotide TJU-2755 encapsulated in pH-sensitive liposomes can be used to effectively reduce endotoxin-mediated production of TNF-alpha in macrophages in vivo and thus may be of value in attenuating or preventing macrophage-mediated liver injury.

Allele-specific histone acetylation accompanies genomic imprinting of the insulin-like growth factor II receptor gene.

The mouse insulin-like growth factor II receptor (Igf2r) gene encodes two reciprocally imprinted RNA transcripts: paternally imprinted Igf2r sense and maternally imprinted Igf2r antisense. Although DNA methylation has been implicated in the initiation and maintenance of genomic imprinting, acetylation of core histones has recently been appreciated as another important factor that regulates gene expression. To determine whether histone acetylation participates in the regulation of Igf2r imprinting, we examined the relative abundance of acetylated histones in interspecific mice (M. spretus x C57BL/6). Oligonucleosomes derived from liver were immunoprecipitated with acetyl-histone antiserum and were analyzed for the allelic distribution of DNA from the region of the sense and antisense Igf2r promoters. In nucleosomes associated with the Igf2r sense promoter, histone acetylation was demonstrated on the maternal allele, which is transcriptionally active. There was much less histone acetylation on the suppressed paternal allele. In nucleosomes associated with the Igf2r antisense promoter, the active paternal allele was heavily acetylated, whereas the suppressed maternal allele was underacetylated. Treatment of cultured fibroblasts with the histone deacetylase inhibitor Trichostatin A induces partial relaxation of genomic imprinting as well as decreased DNA methylation of both Igf2r sense and antisense promoters. These results demonstrate that increases in histone acetylation can lead to decreased DNA methylation, thereby modulating the regulation of the imprinted expression of Igf2r sense and antisense transcripts.

Age-based rationing in the allocation of health care.

OBJECTIVES: This article seeks to review debates about age-based rationing in health care. METHODS: The article identifies four different levels (or types) of decision-making in health resources allocation--societal, strategic, programmatic, and clinical--and assesses how the issues of rationing vary in relation to each level. RESULTS: The article concludes that rationing is least defensible at the clinical level, where it is also most covert. The role of rationing at other levels is more defensible when based on grounds of cost-effectiveness rather than equity. The article emphasizes the importance of fairness in health allocation and suggests that efficiency criteria need to be considered in that context. DISCUSSION: The article suggests that rationing is most problematic where it is least overt. This raises further questions about how rationing can be made more explicit at different levels of decision making.

Exploring the interaction of some N-benzyloxycarbonyl-L-phenyl alanyl-L-alanine ketones and bovine spleen cathepsin B by molecular modeling and binding free energy calculation.

A semi-empirical method for estimation of binding free energy, recently proposed by Aqvist and coworkers, has been effectively tested in several protein-ligand binding cases. We have applied this linear interaction energy method to predict the binding of some N-benzyloxycarbonyl-L-phenyl alanyl-L-alanine ketones with bovine cathepsin B and computed the respective absolute binding constants from averages of molecular dynamics simulations. It is found that the computer simulation results agree well with available experimental data and make it possible to understand better the origin of tight binding and inhibitor specificity of cathepsin B.

Effect of antithyroid drugs on hydroxyl radical formation and alpha-1-proteinase inhibitor inactivation by neutrophils: therapeutic implications.

The release of proteolytic enzymes and generation of strong oxidants such as the hydroxyl radical by activated neutrophils has been proposed to play an important role in mediating toxin-induced liver injury. The antithyroid drug propylthiouracil protects against liver injury induced by many hepatotoxic agents and markedly reduces mortality in patients with alcoholic liver disease. However, the mechanism(s) by which propylthiouracil protects against liver injury is not well understood. The present studies investigate the effect of antithyroid drugs on proteolytic enzyme activity and on hydroxyl radical generation from activated neutrophils. In the presence of hydrogen peroxide and chloride, neutrophil myeloperoxidase, an enzyme from the same gene superfamily as thyroid peroxidase, generates hypochlorous acid which inactivates alpha-1-proteinase inhibitor (A1PI) present in serum. This inactivation allows neutrophil-released proteolytic enzymes to attack cells. In the present study myeloperoxidase activity was inhibited fully at therapeutic concentrations by antithyroid drugs (propylthiouracil and methimazole). Antithyroid drugs fully prevented hypochlorous acid formation, and prevented neutrophil-mediated inactivation of A1PI, with concomitant blockage of proteolytic activity. Conversely, generation of both superoxide and hydroxyl radicals by activated neutrophils was unaffected by propylthiouracil. The production of these oxygen radicals was fully inhibited by the NADPH oxidase inhibitor diphenylene iodonium chloride, however. These studies indicate that antithyroid drugs are unlikely to prevent cell injury by inhibiting hydroxyl radical generation or by scavenging hydroxyl radicals, but are likely to exert their hepatoprotective anti-inflammatory action by inhibiting neutrophil myeloperoxidase, an enzyme akin to thyroid peroxidase.

The mechanism of inhibitory effect of eicosapentaenoic acid on phagocytic activity and chemotaxis of human neutrophil granulocytes.

Free eicosapentaenoic acid (EPA) was found to inhibit dose dependently the chemiluminescence of human neutrophil granulocytes phagocytosing zymosan and their chemotaxis induced by C5a-containing zymosan-activated serum (ZAS) and platelet-activating factor. Rigidification of plasma membranes in the ZAS-treated cells could be observed by measuring the fluorescence anisotropy. The cells were labeled by 3-[p-(6-phenyl-1,3,5-hexatrienoil) phenyl] propionic acid, reporting plasma membrane for determination of membrane fluidity. In resting, nonstimulated neutrophils, EPA dose dependently increased the fluidity of plasma membrane. In zymosan-activated cells, however, after a short fluidization, the basic effect of EPA was a rigidification compared to very low fluorescence anisotropy values of activated control cells. This diminished fluidity, increased membrane stability of plasma membranes can be one of the reasons for the decreased functions (phagocytosis and chemotaxis) of human EPA-treated neutrophils.

Molecular architecture and biophysical properties of phospholipids during thermal adaptation in fish: an experimental and model study.

Phospholipids from livers of carps (Cyprinus carpio L.) adapted to winter (5 degrees C) and summer (25 degrees C) temperatures were isolated, and the fatty acid composition of total phospholipids, as well as molecular species composition of diacyl phosphatidylcholines and ethanolamines, were determined. Order parameter of 5-doxyl stearic acid and steady-state fluorescence anisotropy of different anthroyloxy fatty acids--[2-, 12(N-9-anthroyloxy)stearic acid and 16(N-9-anthroyloxy)palmitic acid--embedded in native and synthetic (16:0/16:0, 16:0/22:6, 18:0/22:6, 18:1/22:6, 20:4/20:4, 22:6/22:6 phosphatidylcholines and 16:0/18:1, 18:1/22:6 phosphatidylethanolamines) phospholipid vesicles was also determined between -30 and 30 degrees C and 5 and 30 degrees C, respectively. There is an accumulation of 1-monoenoic, 2-polyenoic diacyl phosphatidylcholine and ethanolamine with a concomitant reduction of 1-stearoyl,2-docosahexaenoyl species in the cold-adapted state. Despite a 30% accumulation of long-chain polyunsaturated fatty acids in phospholipids in cold, there is only a 5 degrees C downshift in the solid-gel to liquid-crystalline phase transition temperature (-8 vs. -13 degrees C). Vesicles from total phospholipids of cold-adapted fish proved to be more disordered in all segments than from the warm-adapted ones when assayed using 2,12-(N-9-anthroyloxy)stearic and 16-(N-9-anthroyloxy)palmitic acid. Vesicles made from purified phosphatidylcholines showed the same pattern, but they were more disordered than the corresponding total phospholipids. This could be modelled using mixed phospholipid vesicles made of synthetic 16:0/22:6 phosphatidylcholine (75%) and either 18:1/22:6 phosphatidylethanolamine (25%) vs. 16:0/18:1 phosphatidylethanolamine (25%) and comparison of the anisotropy parameters of 100% 16:0/22:6 and 100% 18:1/22:6 phosphatidylcholine vesicles. Mixing either 16:0/18:1 (25%) or 18:1/22:6 (25%) phosphatidylethanolamines to 18:0/22:6 (75%) phosphatidylcholine shifted down or up, respectively, the transition temperature of vesicles compared to 100% 18:0/22:6 vesicles assayed by electron spin resonance spectroscopy using 5-doxylstearic acid. It is concluded that it is not the gross amount of long-chain polyunsaturated fatty acids in phospholipids, but rather their specific combination with cis delta 9 monounsaturated fatty acids in the position sn-1, especially in phosphatidylethanolamines, that is important in determining the physical properties of biomembranes in relation to adaptational temperature.

Determining one or more change points.

A statistical method is presented for determining whether a line has one or more change points at unknown locations. A change point is a point where a line suddenly changes its slope but is continuous, i.e. it does not jump. Change points are also referred to as break points or join points. A step-wise procedure is suggested which starts by fitting a straight line without points. Next a line with a single change point is fit to the data, and a statistical test is used to determine if the line with a single change point provides a significantly better fit to the data than the line with no change points. This can then be followed by fitting a line with two change points, etc. The problem of determining the number of change points that best fits the data is discussed. A modified version of Akaike's information criterion (AIC) is used to select the best number of change points to avoid over fitting. An example of fluorescence anisotropy measurements of the total phospholipid from the liver of a marine fish as a function of temperature is presented.

Erythrocyte lipids in triose-phosphate isomerase deficiency.

Marked hypoalphalipoproteinemia was found together with relatively low serum cholesterol, triacylglycerol, and LDL levels in a triose-phosphate isomerase (TPI; D-glyceraldehyde-3-phosphate ketol-isomerase, EC 5.3.1.1)-deficient Hungarian family, especially in the two compound-heterozygote brothers. Apart from a slight increase in palmitic and stearic acids together with a slight decrease in oleic and linoleic acids, no other changes were found in the fatty acid composition of the erythrocyte phospholipids. Anisotropy measurements with n-(9-anthroyloxy) stearic and -palmitic acid fluorophores revealed increased motional freedom of the fatty acid chains in the external lipid layers of the intact erythrocytes from all members of the TPI-deficient family as compared with normal age-matched controls. This asymmetric increase in membrane fluidity was found to be significantly higher in the propositus than in his compound-heterozygote brother without any neurological disorders. The change in membrane fluidity may result from as-yet-unresolved aspects of the lipid composition of the plasma membrane. Our findings that the differences between the TPI-deficient individuals and normal controls and the differences between the two compound-heterozygote brothers were all absent in the phospholipid extracts of the same erythrocytes favor the assumption that the increased motional freedom of the fatty acid chains in the external surface of the bilayer is caused by the binding of the mutant TPI molecule to the N-terminal sequence of band 3 protein.

Structural order of membranes and composition of phospholipids in fish brain cells during thermal acclimatization.

A comparison of the structural orders of membranes of a mixed brain-cell population isolated from Cyprinus carpio L. acclimated to either summer (23-25 degrees C) or winter (5 degrees C) revealed a high degree of compensation (80%) for temperature, as assayed by electron spin resonance spectroscopy. The cells rapidly forget their thermal history and adjust the physical properties of the membranes when shifted to the other extreme of temperature either in vivo or in vitro. Phospholipids separated from both types of animals exhibit only around 10% compensation. Arachidonic and docosahexaenoic acids are the major polyunsaturated fatty acids in the brains, but the fatty acid composition of the brain total phospholipids does not vary with adaptation to temperature. Separation of phosphatidylcholines and phosphatidylethanolamines into molecular species revealed a 2- to 3-fold accumulation of 18:1/22:6, 18:1/20:4, and 18:1/18:1 species in the latter; 18:0/22:6 showed an opposite tendency. Molecular species composition of phosphatidylcholines did not vary with the temperature. The same trends of changes were seen with brains of freshwater fish from subtropical (Catla catla L.) or boreal (Acerina cernua) regions. It is concluded that the gross amount of docosahexaenoic acid (22:6) plays only a minor role in adjusting the membrane physical properties to temperature. Factors other than lipids might be involved in the adaptation processes. Due to their specific molecular architecture, molecules such as 18:1/22:6, 18:1/20:4, or 18:1/18:1 phosphatidylethanolamine might prevent the contraction of membranes in the cold and may provide an environment for some other components involved in the temperature regulation of physical properties of nerve cell membranes.

Role of phospholipid molecular species in maintaining lipid membrane structure in response to temperature.

The compositions and physical states of the liver phospholipids of fish and phospholipids of shrimps adapted to relatively constant but radically different temperatures were investigated. There were no measurable differences in their gross fatty acid compositions of phospholipids from the species obtained from identical temperature. Saturated-to-unsaturated fatty acid ratio did not show any convincing difference. Docosahexaenoic acid (22:6) did not seem to participate in the process of adaptation. Cold adaptation was coincidental with oleic acid (18:1) accumulation, preferentially in the phosphatidylethanolamine. In the experiment with rats, it has been found that the fish oil fed rats showed a similarity in their liver phospholipid fatty acid composition like fish liver phospholipids. Determination of molecular species composition of phosphatidylcholine and phosphatidylethanolamine revealed a 4- to 5-fold and 10-fold increase in the level of 18:1/22:6 and 18:1/20:5 species respectively in favor of cold adaptation. Phospholipids from cold-adapted species showed a more fluid structure than that of warm-adapted species near the C-2 segment of the bilayer, but not in the deeper regions. Phospholipids from the rat livers did not show any change irrespective of diet. Phosphatidylcholines from rat liver, fish liver or shrimps did not show any difference among them in their fluidity irrespective of their environmental conditions or diet. An appropriate combination (75:25) of phosphatidylcholine from rat liver with phosphatidylethanolamines from cold adapted species showed a drastic fluidization at the C-2 segment, in comparison with their phosphatidylcholines.(ABSTRACT TRUNCATED AT 250 WORDS)

Platelet membrane fluidity and plasma malondialdehyde levels in Alzheimer's demented patients with and without family history of dementia.

Platelet membrane fluidity (PMF) was measured with three different fluorescent probes, 1,6-diphenyl-1,3,5-hexatriene (DPH), 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH), 3-(p-phenyl-1,3,5-hexatrienyl)phenyl-propionic acid (DPH-PA), which labeled different parts of the bilayer (the hydrophobic core and the positively and negatively charged regions, respectively) in Alzheimer's disease (AD) patients with and without a family history of dementia, and in a control group. In support of earlier findings in the literature, significantly increased PMF was found by the application of DPH in both groups with AD. The use of the fluorescence probe TMA-DPH, however, revealed no differences between the groups. In contrast, significant rigidification was observed with DPH-PA, but only in the AD group with a positive family history of dementia. The plasma malondialdehyde levels appeared to be similar in each group. Our findings are discussed in light of the controversies regarding the value of PMF measurements in AD.

Effects of Temperature and Dietary Lipids on Phospholipid Fatty Acids and Membrane Fluidity in Steinernema carpocapsae.

The phospholipid composition of Steinernema carpocapsae was studied in relation to diet and culture temperature. When reared at 18 and 27.5 C on Galleria mellonella or on an artificial diet supplemented with lard, linseed oil, or fish oil as lipid sources, nematode phospholipids contained an abundance of 20-carbon polyunsaturated fatty acids, with eicosapentaenoic acid (20:5(n - 3)) predominant, regardless of the fatty acid composition of the diet. Because the level of linolenic acid (18:3(n - 3)) in nematode phospholipids was very low and because eicosapentaenoic acid was present even when its precursor (linolenic acid) was undetectable in the diet, S. carpocapsae likely produces n - 3 polyunsaturated fatty acids by de novo biosynthesis, a pathway seldom reported in eukaryotic animals. Reduction of growth temperature from 25 to 18 C increased the proportion of 20:5(n - 3) but not other polyunsaturated fatty acids. A fluorescence polarization technique revealed that vesicles produced from phospholipids of nematodes reared at 18 C were less ordered than those from nematodes reared at 27.5 C, especially in the outermost region of the bilayer. Dietary fish oil increased fluidity in the outermost region but increased rigidity in deeper regions. Therefore, S. carpocapsae appears to modify its membrane physical state in response to temperature, and eicosapentaenoic acid may be involved in this response. The results also indicate that nematode membrane physical state can be modified dietarily, possibly to the benefit of host-finding or survival of S. carpocapsae at low temperatures.

Use of a rule based graph-theoretical system in evaluating the activity of a class of nucleoside analogues against human immunodeficiency virus.

A rule based graph-theoretical system has been used to evaluate qualitatively the activity of a class of nucleoside analogues against human immunodeficiency virus (HIV). The system identifies biologically relevant vertices (atoms) in the molecular graphs of the compounds which have the biological activity of interest. The idea is to relate biological activity with the structural or substructural characteristics of the compounds from the point of view of molecular topology (connectivity). The system brings vertices of similar or close topological environment in the respective compounds together and this is reflected in the ranges of values formed by a distance based index of the vertices, the 'distance exponent index (Dx)', where x is any real number. It is found that the system makes correct prediction of the activity of all the compounds (active as well as inactives) of both training set and the test set against HIV. It is also apparent from this study that the index D-4, which has been used here, can make a useful classification of the vertices according to their molecular environment and the system can produce significant result in a small as well as diverse data base.

Molecular and structural composition of phospholipid membranes in livers of marine and freshwater fish in relation to temperature.

The compositions and physical states of the liver phospholipids of marine and freshwater fish adapted to relatively constant but radically different temperatures were investigated. Fish adapted to low temperature (5-10 degrees C) accumulated more unsaturated fatty acids than those in a warm (25-27 degrees C) environment. There were no measurable differences in the gross fatty acid compositions of the total liver phospholipids from identical thermal environments. Docosahexaenoic acid (22:6) did not seem to participate in the process of adaptation. Cold adaptation was coincidental with oleic acid (18:1) accumulation, preferentially in the phosphatidylethanolamine. Determination of the molecular species composition of phosphatidylethanolamine revealed a 2- to 3-fold and 10-fold increase in the level of 18:1/22:6 and 18:1/20:5 species, respectively. ESR spectroscopy revealed a 7-10% compensation in the ordering state of native phospholipids with temperature. Combination of 16:0/22:6 phosphatidylcholine with phosphatidylethanolamines of cold-adapted marine fish showed a drastic fluidization near the C-2 segment of the bilayer, but not in the deeper regions. An appropriate combination (75:25) of phosphatidylcholines from warmth-adapted marine fish with phosphatidylethanolamines from cold-adapted marine fish mimicked a 100% adaptational efficacy in the C-2 segment as compared with the phosphatidylethanolamines of warmth-adapted marine fish. A specific role of 18:1/22:6 phosphatidylethanolamine in controlling membrane structure and physical state with thermal adaptation is proposed.