Review of Eukaryote Cellular Membrane Lipid Composition, with Special Attention to the Fatty Acids.

Biological membranes, primarily composed of lipids, envelop each living cell. The intricate composition and organization of membrane lipids, including the variety of fatty acids they encompass, serve a dynamic role in sustaining cellular structural integrity and functionality. Typically, modifications in lipid composition coincide with consequential alterations in universally significant signaling pathways. Exploring the various fatty acids, which serve as the foundational building blocks of membrane lipids, provides crucial insights into the underlying mechanisms governing a myriad of cellular processes, such as membrane fluidity, protein trafficking, signal transduction, intercellular communication, and the etiology of certain metabolic disorders. Furthermore, comprehending how alterations in the lipid composition, especially concerning the fatty acid profile, either contribute to or prevent the onset of pathological conditions stands as a compelling area of research. Hence, this review aims to meticulously introduce the intricacies of membrane lipids and their constituent fatty acids in a healthy organism, thereby illuminating their remarkable diversity and profound influence on cellular function. Furthermore, this review aspires to highlight some potential therapeutic targets for various pathological conditions that may be ameliorated through dietary fatty acid supplements. The initial section of this review expounds on the eukaryotic biomembranes and their complex lipids. Subsequent sections provide insights into the synthesis, membrane incorporation, and distribution of fatty acids across various fractions of membrane lipids. The last section highlights the functional significance of membrane-associated fatty acids and their innate capacity to shape the various cellular physiological responses.

Comparison of Antibacterial Activities of Korean Pine (Pinus densiflora) Needle Steam Distillation Extract on Escherichia coli and Staphylococcus aureus Focusing on Membrane Fluidity and Genes Involved in Membrane Lipids and Stress.

The antibacterial activity and mechanism of Pinus densiflora extracts against Escherichia coli and Staphylococcus aureus were investigated. The growth inhibition tests of paper diffusion and optical density exhibited that the extracts have potent antibacterial potentials against foodborne pathogens. The measurement of membrane fluidity by fluorescence polarization has indicated that one of the antibacterial mechanisms involves the disruption of membrane integrity resulting in an increase in the membrane fluidity in both of E. coli and S. aureus. The alteration of fatty acid composition was accompanied by the disturbance of membranes thus shifting the proportion of saturated verses unsaturated fatty acids or trans fatty acids from 1.27:1 to 1.35:1 in E. coli and 1.47:1 to 2.31:1 in S. aureus, most likely to compensate for the increased membrane fluidity by means of a higher proportion of saturated fatty acids which is known to render rigidity in membranes. Realtime q-PCR (polymerase chain reaction) analysis of fatty acid synthetic genes and bacterial stress genes revealed that there was minimal influence of P. densiflora extracts on fatty acid genes except for fab I and the stress rpos in E. coli, and relatively greater impact on fatty acid genes and the stress sigB in S. aureus.

The Impact of Short-Term Shark Liver Oil Supplementation on the Fatty Acid Composition of Erythrocyte Membranes.

Fatty acid (FA) balance is strictly related to human health. The composition of fatty acids in lipid membranes seems to be influenced by diet. Shark liver oil (SLO) supplementation has been widely used recently in the prevention and treatment of human diseases. We analyzed the impact of short-term SLO supplementation on certain biochemical parameters and erythrocyte FA composition in a group of young healthy women. Our results showed that 6 weeks of SLO supplementation led to a significant decrease in C-reactive protein levels in sera and intracellular cholesterol levels in peripheral blood mononuclear cells. SLO supplementation caused a significant increase in the content of the polyunsaturated omega-3 FAs: docosahexaenoic acid, docosapentaenoic acid and α-linolenic acid. In the group of omega-6 FAs, we observed a significant elevation of arachidonic and dihomo-gamma-linoleic acid content. Due to these alterations, the omega-3 index increased significantly from 3.6% (before) to 4.2% (after supplementation). We also observed the impact of SLO supplementation on the membrane fluidity index. The ratio between saturated and unsaturated FAs decreased significantly from 13.1 to 9.9. In conclusion, our results show that even short-term SLO supplementation can improve human erythrocyte fatty acid composition and other parameters that may have health-promoting consequences.

Branched chain fatty acid synthesis drives tissue-specific innate immune response and infection dynamics of Staphylococcus aureus.

Fatty acid-derived acyl chains of phospholipids and lipoproteins are central to bacterial membrane fluidity and lipoprotein function. Though it can incorporate exogenous unsaturated fatty acids (UFA), Staphylococcus aureus synthesizes branched chain fatty acids (BCFA), not UFA, to modulate or increase membrane fluidity. However, both endogenous BCFA and exogenous UFA can be attached to bacterial lipoproteins. Furthermore, S. aureus membrane lipid content varies based upon the amount of exogenous lipid in the environment. Thus far, the relevance of acyl chain diversity within the S. aureus cell envelope is limited to the observation that attachment of UFA to lipoproteins enhances cytokine secretion by cell lines in a TLR2-dependent manner. Here, we leveraged a BCFA auxotroph of S. aureus and determined that driving UFA incorporation disrupted infection dynamics and increased cytokine production in the liver during systemic infection of mice. In contrast, infection of TLR2-deficient mice restored inflammatory cytokines and bacterial burden to wildtype levels, linking the shift in acyl chain composition toward UFA to detrimental immune activation in vivo. In in vitro studies, bacterial lipoproteins isolated from UFA-supplemented cultures were resistant to lipase-mediated ester hydrolysis and exhibited heightened TLR2-dependent innate cell activation, whereas lipoproteins with BCFA esters were completely inactivated after lipase treatment. These results suggest that de novo synthesis of BCFA reduces lipoprotein-mediated TLR2 activation and improves lipase-mediated hydrolysis making it an important determinant of innate immunity. Overall, this study highlights the potential relevance of cell envelope acyl chain repertoire in infection dynamics of bacterial pathogens.

Menaquinone-mediated regulation of membrane fluidity is relevant for fitness of Listeria monocytogenes.

Listeria monocytogenes is a food-borne pathogen with the ability to grow at low temperatures down to - 0.4 °C. Maintaining cytoplasmic membrane fluidity by changing the lipid membrane composition is important during growth at low temperatures. In Listeria monocytogenes, the dominant adaptation effect is the fluidization of the membrane by shortening of fatty acid chain length. In some strains, however, an additional response is the increase in menaquinone content during growth at low temperatures. The increase of this neutral lipid leads to fluidization of the membrane and thus represents a mechanism that is complementary to the fatty acid-mediated modification of membrane fluidity. This study demonstrated that the reduction of menaquinone content for Listeria monocytogenes strains resulted in significantly lower resistance to temperature stress and lower growth rates compared to unaffected control cultures after growth at 6 °C. Menaquinone content was reduced by supplementation with aromatic amino acids, which led to a feedback inhibition of the menaquinone synthesis. Menaquinone-reduced Listeria monocytogenes strains showed reduced bacterial cell fitness. This confirmed the adaptive function of menaquinones for growth at low temperatures of this pathogen.

Green tea extract-biomembrane interaction study: The role of its two major components, (-)-epigallocatechin gallate and (-)-epigallocatechin.

The interaction of antioxidants with biological membranes is closely related with their efficacy to inhibit the lipid peroxidation, the cause of several pathologies including cancer, neurodegenerative and cardiovascular disorders. Despite being pointed as a promising antioxidant agent by some authors, the anti-lipid peroxidation of green tea extract (GTE) has not aroused consensus among the scientific community. Since the interaction of drugs with biological membranes plays a key role on their therapeutic activity, this study aims to evaluate the interaction of GTE with liposomes as in vitro biomembrane models composed of 1,2-dimyristoyl-sn-glycero-3-phosphocholine phospholipids in the absence and presence of cholesterol (CHOL) (15 mol%). The affinity of GTE and its main components (-)-epigallocatechin gallate (EGCG) and (-)-epigallocatechin (EGC) to the lipid bilayer, their membrane location as well as their effect on the membrane fluidity was investigated by diverse biophysical techniques. Derivative spectrophotometry results proved that GTE has high affinity to the membrane by establishing hydrophobic interactions with the non-polar region of phospholipids and electrostatic interactions with the polar phospholipid heads. Fluorescence and dynamic light scattering data confirm that GTE is located in both hydrophobic and hydrophilic regions of the lipid membrane, therefore affecting the structure of the biomembrane by increasing its fluidity. However, the increased stiffness and organization of the lipid bilayer caused by CHOL significantly affected the interaction of GTE with the membrane. Moreover, the obtained findings suggest a direct contribution of EGCG and EGC on the GTE-membrane interaction.

Chemical constituents, antibacterial activity and mechanism of Paeonia suffruticosa Andr. buds extract against Staphylococcus aureus and Escherichia coli O157:H7.

Sixteen chemical constituents of Paeonia suffruticosa Andr. buds extract (PSABE) were identified by UHPLC-PDA-Q/TOF-MS, belonging to phenolic acids, flavonoids, monoterpene glycosides and gallotannins. PSABE exhibited significant antibacterial activity against six tested microorganisms. Particularly, it showed the most efficient antibacterial effect against Staphylococcus aureus and Escherichia coli O157:H7, which the minimum inhibition concentration (MIC) and minimum bactericide concentration (MBC) both were 1.56 mg/mL and 6.25 mg/mL, respectively. The results showed that PSABE induced obvious alterations in membrane fatty acid composition of S. aureus and E. coli O157:H7, such as the decrease of unsaturated fatty acids, leading to the reduce of membrane fluidity. Membrane integrity was destroyed and cell morphology was obviously changed with PSABE. Furthermore, the transcription level of virulence factors was inhibited in the presence of PSABE. These results indicated that PSABE mainly exerted antibacterial effect by damaging cell membrane and inhibiting transcription level of virulence factors.[Figure: see text].

Lipid Profile, Lipoprotein Subfractions, and Fluidity of Membranes in Children and Adolescents with Depressive Disorder: Effect of Omega-3 Fatty Acids in a Double-Blind Randomized Controlled Study.

Depressive disorder (DD) is a psychiatric disorder whose molecular basis is not fully understood. It is assumed that reduced consumption of fish and omega-3 fatty acids (FA) is associated with DD. Other lipids such as total cholesterol (TCH), LDL-, and HDL-cholesterols (LDL-CH, HDL-CH) also play a role in depression. The primary endpoint of the study was the effect of omega-3 FA on the severity of depression in children and adolescents. This study aimed to investigate the secondary endpoint, relationship between depressive disorder symptoms and lipid profile, LDL- and HDL-cholesterol subfractions, Paraoxonase 1 (PON1) activities, and erythrocyte membrane fluidity in 58 depressed children and adolescents (calculated by the statistical program on the effect size), as well as the effect of omega-3 FA on the monitored parameters. Depressive symptoms were assessed by the Children's Depression Inventory (CDI), lipid profile by standard biochemical procedures, and LDL- and HDL-subfractions by the Lipoprint system. Basic biochemical parameters including lipid profile were compared with levels in 20 healthy children and were in the physiological range. Improvement of symptoms in the group supplemented with a fish oil emulsion rich in omega-3 FA in contrast to omega-6 FA (emulsion of sunflower oil) has been observed. We are the first to report that omega-3 FAs, but not omega-6 FA, increase large HDL subfractions (anti-atherogenic) after 12 weeks of supplementation and decrease small HDL subfractions (proatherogenic) in depressed children. We found a negative correlation between CDI score and HDL-CH and the large HDL subfraction, but not LDL-CH subfractions. CDI score was not associated with erythrocyte membrane fluidity. Our results suggest that HDL-CH and its subfractions, but not LDL-CH may play a role in the pathophysiology of depressive disorder. The study was registered under ISRCTN81655012.

Stearoyl-CoA Desaturase-1 Enzyme Inhibition by Grape Skin Extracts Affects Membrane Fluidity in Human Colon Cancer Cell Lines.

The polyphenolic compounds present in grape extracts have chemopreventive and anticancer properties. Here, we studied the ability of two grape skin extracts (GSEs), Autumn Royal and Egnatia, to influence the cell motility and membrane fluidity regulated by the enzyme Stearoyl-CoA desaturase-1 (SCD1) which increases with the cancer aggressiveness. Caco2 and SW480 human colon cancer cell lines were treated with increasing concentrations of GSEs to evaluate cell proliferation and motility. SCD1 levels were evaluated in both treated cell lines, by membrane lipidomic analysis conducted by gas chromatography. The expression levels of SCD1 and other factors involved in the reorganization of the cytoskeleton and focal adhesions were assessed by Real-time PCR, Western Blotting, and Immunofluorescence staining. High-performance liquid chromatography (HPLC) analyses were performed to determine the phenolic composition in the GSEs, finding them more expressed in Autumn Royal than in Egnatia. Both treatments reduced the levels of SCD1, phospho-Rac1/Cdc42/Rac1/Cdc42 ratio, Cofilin, Vimentin, and phospho-Paxillin especially in Caco2 compared to SW480, showing a different behavior of the two cell lines to these natural compounds. Our findings show that GSEs block the cell migration and membrane fluidity through a new mechanism of action involving structural cellular components.

Cultivation at high osmotic pressure confers ubiquinone 8-independent protection of respiration on Escherichia coli.

Ubiquinone 8 (coenzyme Q8 or Q8) mediates electron transfer within the aerobic respiratory chain, mitigates oxidative stress, and contributes to gene expression in Escherichia coli In addition, Q8 was proposed to confer bacterial osmotolerance by accumulating during growth at high osmotic pressure and altering membrane stability. The osmolyte trehalose and membrane lipid cardiolipin accumulate in E. coli cells cultivated at high osmotic pressure. Here, Q8 deficiency impaired E. coli growth at low osmotic pressure and rendered growth osmotically sensitive. The Q8 deficiency impeded cellular O2 uptake and also inhibited the activities of two proton symporters, the osmosensing transporter ProP and the lactose transporter LacY. Q8 supplementation decreased membrane fluidity in liposomes, but did not affect ProP activity in proteoliposomes, which is respiration-independent. Liposomes and proteoliposomes prepared with E. coli lipids were used for these experiments. Similar oxygen uptake rates were observed for bacteria cultivated at low and high osmotic pressures. In contrast, respiration was dramatically inhibited when bacteria grown at the same low osmotic pressure were shifted to high osmotic pressure. Thus, respiration was restored during prolonged growth of E. coli at high osmotic pressure. Of note, bacteria cultivated at low and high osmotic pressures had similar Q8 concentrations. The protection of respiration was neither diminished by cardiolipin deficiency nor conferred by trehalose overproduction during growth at low osmotic pressure, but rather might be achieved by Q8-independent respiratory chain remodeling. We conclude that osmotolerance is conferred through Q8-independent protection of respiration, not by altering physical properties of the membrane.

Understanding toward the Biophysical Interaction of Polymeric Proanthocyanidins (Persimmon Condensed Tannins) with Biomembranes: Relevance for Biological Effects.

Persimmon condensed tannins (PT) are highly polymerized (mDP = 26) and highly galloylated (72%) proanthocyanidins. Its pleiotropic effects in oxidation resistance, neuroprotection, hypolipidemia, and cardio-protection both in vitro and in vivo were widely reported. Because large proanthocyanidins are unlikely to be absorbed in the gastrointestinal tract, it is believed that the interaction of PT with biological membranes may play a crucial role in its biological activities. In the present study, the capacities of PT adsorbing to membrane, partitioning into membrane, and its influence on the membrane fluidity were investigated by fluorescence quenching, isothermal titration calorimetry (ITC) and fluorescence anisotropy measurements in a biomembrane-mimetic system composed of 1-palmitoyl-2-oleoylphosphatidylcholine (POPC), 1-palmitoyl-2-oleoylphosphatidylethanolamine (POPE), sphingomyelin (SPM), and cholesterol (CHOL). Besides, the effects of PT on the morphology and integrity of the cell membrane were studied by scanning electron microscopy (SEM) and fluorescence staining in the 3T3-L1 cell model. The results suggested that PT could affect cell membrane rafts domains, destroy the cell membrane morphology, and regulate cell membrane fluidity, which might contribute to its biological effects.

Attenuation of diabetic nephropathy by dietary fenugreek (Trigonella foenum-graecum) seeds and onion (Allium cepa) via suppression of glucose transporters and renin-angiotensin system.

OBJECTIVES: The aim of this study was to determine the effects of dietary fenugreek (Trigonella foenum-graecum) seeds and onion on the hyperglycemia-stimulated glucose transporters and activation of renin-angiotensin system-mediated cascade of events leading to renal lesions in diabetic animals. METHODS: The mechanistic aspects of nephroprotective influence of dietary fenugreek seeds (10%) and onion (3%) on diabetic renal lesions was investigated in streptozotocin diabetic rats. Renal damage was assessed by measuring proteinuria, enzymuria, expression of glucose transporters, renin-angiotensin system, and activities of polyol pathway enzymes. RESULTS: Diabetes resulted in an upregulation of glucose transporters in kidney tissue, which was countered by these dietary interventions. The upregulation of renal angiotensin-converting enzyme and its receptor was also countered by these dietary interventions. Dietary fenugreek and onion significantly reduced metabolites of polyol pathway, nitric oxide, and N-acetyl-ß-d-glucosaminidase activity. Markers of podocyte damage in kidney (nephrin, podocin, and podocalyxin) and their urinary excretion were normalized along with downregulation of the expression of kidney injury molecule-1 by these dietary interventions. Dietary fenugreek and onion effectively countered the diabetes-induced structural abnormalities of renal tissue. CONCLUSION: Feeding fiber-rich fenugreek seeds and sulfur compounds-rich onion produced a blockade in glucose translocation and renin-angiotensin system in the early stage of diabetic nephropathy. This involved a downregulation of the expression of polyol pathway enzymes, partial restoration of the podocyte damage, revival of renal architecture and functional abnormality. The present study also suggested that these two dietary interventions offer a higher renoprotective influence when consumed together.

An Electron paramagnetic resonance (EPR) spin labeling study in HT-29 Colon adenocarcinoma cells after Hypericin-mediated photodynamic therapy.

BACKGROUND: Colon cancer affects 1.23 million people worldwide and is the third most common malignant disease in men and the second in women. The only curative treatment is surgical resection, but a significant number of patients develop local recurrence or distant metastases. One of the alternative treatment methods for colon cancer is photodynamic therapy (PDT). In recent years, hypericin (HYP) derived from Hypericum perforatum has been suggested as a strong candidate photosensitizer for PDT. Our interest is focused on the biophysical changes in colon cancer cells in relation to HYP-mediated PDT. RESULTS: In this study, HYP-mediated PDT at 0.04, 0.08 or 0.15 µM HYP concentrations was performed in HT-29 colon adenocarcinoma cells and the Electron Paramagnetic Resonance (EPR) spectra of the spin labeled cells were obtained. Plasma membranes are already heterogeneous structures; the presence of cancer cells increased the heterogeneity and also fluidity of the plasma membranes. Therefore, the obtained spectra were evaluated by EPRSIMC program, which provides the calculation of heterogeneous structures up to four spectral components with different fluidity characteristics. Generally, two motional patterns were obtained from calculations and the number of them increased at the highest concentration. As the order parameters of the most populated components compared, an increase was observed depending on the HYP concentration. However, because of the heterogeneous structure of membrane, the order parameters of the less populated components did not exhibit a regular distribution. CONCLUSION: After HYP-mediated PDT, concentration dependent changes were observed in the domain parameters indicating an increase in the HYP accumulation.

The activity of the saponin ginsenoside Rh2 is enhanced by the interaction with membrane sphingomyelin but depressed by cholesterol.

The membrane activity of some saponins, such as digitonin or alpha-hederin, is usually attributed to their interaction with membrane cholesterol (Chol). This contrasts with our recent publication showing that Chol, contrary to sphingomyelin (SM), can delay the cytotoxicity of the saponin ginsenoside Rh2, challenging the usual view that most saponins mediate their membrane effects through interaction with Chol. The aim of the present study was to elucidate the respective importance of Chol and SM as compared to phosphatidylcholine (PC) species in the membrane-related effects of Rh2. On simple lipid monolayers, Rh2 interacted more favorably with eggSM and DOPC than with Chol and eggPC. Using Large Unilamellar Vesicles (LUVs) of binary or ternary lipid compositions, we showed that Rh2 increased vesicle size, decreased membrane fluidity and induced membrane permeability with the following preference: eggSM:eggPC > eggSM:eggPC:Chol > eggPC:Chol. On Giant Unilamellar Vesicles (GUVs), we evidenced that Rh2 generated positive curvatures in eggSM-containing GUVs and small buds followed by intra-luminal vesicles in eggSM-free GUVs. Altogether, our data indicate that eggSM promotes and accelerates membrane-related effects induced by Rh2 whereas Chol slows down and depresses these effects. This study reconsiders the theory that Chol is the only responsible for the activity of saponins.

Biophysical characterization of mycobacterial model membranes and their interaction with rifabutin: Towards lipid-guided drug screening in tuberculosis.

Lipid structure critically dictates the molecular interactions of drugs with membranes influencing passive diffusion, drug partitioning and accumulation, thereby underpinning a lipid-composition specific interplay. Spurring selective passive drug diffusion and uptake through membranes is an obvious solution to combat growing antibiotic resistance with minimized toxicities. However, the spectrum of complex mycobacterial lipids and lack thereof of suitable membrane platforms limits the understanding of mechanisms underlying drug-membrane interactions in tuberculosis. Herein, we developed membrane scaffolds specific to mycobacterial outer membrane and demonstrate them as improvised research platforms for investigating anti-tubercular drug interactions. Combined spectroscopy and microscopy results reveal an enhanced partitioning of model drug Rifabutin in trehalose dimycolate-containing mycobacterial membrane systems. These effects are apportioned to specific changes in membrane structure, order and fluidity leading to enhanced drug interaction. These findings on the membrane biophysical consequences of drug interactions will offer valuable insights for guiding the design of more effective antibiotic drugs coupled with tuned toxicity profiles.

Ameliorative effect of zinc supplementation on compromised small intestinal health in streptozotocin-induced diabetic rats.

Zinc depletion during diabetes postulates a role for zinc nutrition in the management of associated complications. The present study evaluated zinc supplementation for countering the compromised intestinal integrity through moderation of oxidative stress and suppression of stress-stimulated inflammatory proliferation in streptozotocin-induced diabetic rats. Diabetic rats were provided with supplemental zinc for six weeks (5 and 10-times of normal level). Supplemental zinc nurtured diabetic groups evidenced a significant reversal of the disruption of intestinal ultra structure. While the brush border membrane (BBM) of diabetic animals showed decreased fluidity with increased cholesterol: phospholipid ratio and altered polyunsaturated to saturated fatty acid ratio, the same was countered in zinc supplementation. A stimulated activity of BBM-bound enzymes suggested a modulation in membrane dynamics in diabetic condition which was moderated in zinc treatment. Higher expression of the lipid oxidative markers, oxidative stress markers, concomitant inflammatory markers, cytokines, fibrosis factors and apoptotic regulatory proteins in the intestines were curbed by zinc supplementation. The pathological aberrations of the intestinal architecture in diabetic animals were similarly reverted. Thus, supplemental zinc has a favourable consequence in restricting the compromised intestinal health in diabetes which was exerted through a defensive stimulus on oxidative stress induced cytokines, inflammatory propagation, and subsequent injury.

St John's wort extract influences membrane fluidity and composition of phosphatidylcholine and phosphatidylethanolamine in rat C6 glioblastoma cells.

BACKGROUND: Chronic stress, an important factor in the development of depressive disorders, leads to an increased formation of cortisol, which causes a hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis. In addition, cortisol mediates an adaptive effect on plasma membrane fluidity which may affect signal transduction of membrane-bound receptors and contribute to pathophysiological changes. METHODS: Membrane fluidity was measured by fluorescence anisotropy using DPH (1,6-diphenyl-1,3,5-hexatriene) and TMA-DPH (1-(4-(trimethylamino)phenyl)-6-phenylhexa-1,3,5-triene). Changes in cellular content of phosphatidylcholine species was determined by pulse-chase experiments using deuterated choline and mass spectrometry. Single molecule tracking was used to examine the lateral mobility of ß1-adrenoceptors and changes in cAMP formation were measured by ELISA. RESULTS: Chronic exposure (6 - 8 days) of C6 cells to cortisol dose-dependently decreased DPH and TMA-DPH fluorescence anisotropy, reflecting increased membrane fluidity. In contrast, cells pretreated with St. John's wort extract Ze117 showed increased DPH and TMA-DPH fluorescence anisotropy values, indicating a membrane rigidification effect which was mediated at least by the constituents hypericin, hyperforin, quercetin, amentoflavone and biapigenin. The observed membrane fluidizing effect of cortisol could be reversed by cotreatment with Ze117. The membrane rigidification of Ze117 was in line with the in parallel observed decrease in the phosphatidylcholine/phosphatidylethanolamine ratio determined in whole cell lipid extracts. Interestingly, pulse-chase experiments demonstrated, that Ze117 inhibited the incorporation of choline-D9 in phosphatidylcholine species with saturated or monounsaturated fatty acids compared to control cells, while the synthesis of phosphatidylcholine species with polyunsaturated fatty acids was not affected. C6 cells whose membranes have become more rigid by Ze117 showed altered lateral mobility of ß1-adrenoceptors as well as reduced cAMP formation after stimulation with the ß1-adrenoceptor agonist dobutamine. CONCLUSION: Obviously, the signaling of ß1-adrenoceptors depends on the nature of the membrane environment. It can therefore be assumed that Ze117 has a normalizing effect not only on the membrane fluidity of "stressed" cells, but also on lateral mobility and subsequently on the signal transduction of membrane-associated receptors.

Effect of esters based on terpenoids and GABA on fluidity of phospholipid membranes.

The influence of esters based on gamma-aminobutyric acid (GABA) and mono-/bicyclic terpenoids on membrane structure was investigated. The mechanism of action for terpenoid esters on phospholipids of artificial membranes and lipids isolated from the rat stratum corneum was studied by fluorescence and FT-IR spectroscopy. We report here, that inclusion of monocyclic terpenoid esters in phospholipid liposomes leads to growth of excimer to monomer ratio (IE/IM) indicating a decrease of membrane microviscosity. Another mechanism of influence on biomembranes was proposed for ester of bicyclic borneol - in this case a high ratio of vibronic peak intensities (I1/I3) was revealed. The addition of terpenoid esters appears in the FT-IR spectra as intensity reduction of absorption bands associated with C = O, P = O and P-O-С groups of lecithin phospholipids. Similar results were obtained after esters addition to lipids isolated from stratum corneum indicating a decrease of hydrogen bonds number between polar groups of lipids. Thus, the influence of terpenoid esters on molecular organization of the lipid matrix substantiates the feasibility of their use after transdermal delivery in vivo.

Interrelationships between Fatty Acid Composition, Staphyloxanthin Content, Fluidity, and Carbon Flow in the Staphylococcus aureus Membrane.

Fatty acids play a major role in determining membrane biophysical properties. Staphylococcus aureus produces branched-chain fatty acids (BCFAs) and straight-chain saturated fatty acids (SCSFAs), and can directly incorporate exogenous SCSFAs and straight-chain unsaturated fatty acids (SCUFAs). Many S. aureus strains produce the triterpenoid pigment staphyloxanthin, and the balance of BCFAs, SCSFAs and staphyloxanthin determines membrane fluidity. Here, we investigated the relationship of fatty acid and carotenoid production in S. aureus using a pigmented strain (Pig1), its carotenoid-deficient mutant (Pig1ΔcrtM) and the naturally non-pigmented Staphylococcus argenteus that lacks carotenoid biosynthesis genes and is closely related to S. aureus. Fatty acid compositions in all strains were similar under a given culture condition indicating that staphyloxanthin does not influence fatty acid composition. Strain Pig1 had decreased membrane fluidity as measured by fluorescence anisotropy compared to the other strains under all conditions indicating that staphyloxanthin helps maintain membrane rigidity. We could find no evidence for correlation of expression of crtM and fatty acid biosynthesis genes. Supplementation of medium with glucose increased SCSFA production and decreased BCFA and staphyloxanthin production, whereas acetate-supplementation also decreased BCFAs but increased staphyloxanthin production. We believe that staphyloxanthin levels are influenced more through metabolic regulation than responding to fatty acids incorporated into the membrane.