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PubMedDate not supplied

[Dynamics of structural changes in rat liver after single dose of gamma-irradiation].

Histological changes and alterations in biophysical and biochemical parameters in liver of gamma-irradiate rats have been investigated. The gamma-irradiation of the whole body of rats with a single dose of 1 Gy did not cause any impairments of beam structure of rat liver, but resulted in the lymphocytic infiltrations of portal tracts which were not accompanied by formation of spotty areas of necrosis in adjacent areas of lever parenchyma. gamma-Irradiation stimulated proliferation of the hepatocytes and induced time-dependent mitochondrial structure lesions. Post-irradiation changes in cell cytoplasm appeared as disordering in reticulum-endothelial system, among them enlarging and fragmentation of its cisterns, cytoplasmic vacuolization, enhancement of the number of lysosomes and of the lipid inclusion contents. These facts revealed the mobilization of the additional energy resources for recovery of metabolic processes in rat liver. Post-irradiation increase of the level of the hepatocyte membrane lipid peroxidation products preceded liver morphological alterations. The membrane lipid microviscosity decreased in 1 and 3 days after irradiation. As a result of damages of hepatocyte membrane, the activity of the alanin- and asparagin-aminotransferases in blood serum increased 6 hours after. We can conclude that the whole body single gamma-irradiation with a dose of 1 Gy leads to the reversible but significant damages to the rat liver cell membrane structures. These damages might be the reason of radiation-induced liver morphological alterations.

Analysis of Variance↗
PubMed2006

Changes in the prooxidant and antioxidant status of tissues during paraneoplastic processes.

Electron paramagnetic resonance was used to identify paramagnetic centers in the blood and liver of laboratory rats with S-45 sarcoma and mice with Ehrlich carcinoma. Paraneoplastic changes in prooxidant and antioxidant activity of the blood and liver tissue, mitochondrial respiration, and NO metabolism and inhibition of antioxidant processes contribute to impairment of cell membrane structures, erythrocyte hemolysis, and hypoxia. An important role of these processes in the pathogenesis of paraneoplastic anemia is confirmed by the positive effect of antioxidant and membrane-stabilizing therapy.

Anemia↗
PubMed1993

Fatty acids, inflammation and immune responses.

Evidence obtained from experiments in vitro and in vivo suggests that certain unsaturated fatty acids (FA) may be safe and effective antiinflammatory and immunomodulatory agents. Generation of a unique eicosanoid profile with different biological effects by administration of FA precursors other than arachidonic acid is one approach under investigation. In addition to their role as eicosanoid precursors, FA are of major importance in maintaining cell membrane structure, are key determinants of membrane bound enzyme activity and receptor expression. FA can exert these functions directly and therefore may themselves be important regulators of immune responses. For example, certain FA influence cytokine production and proliferation of human T lymphocytes in a manner that is direct and not due to their conversion to eicosanoids. The observations indicate that FA can modulate immune responses by acting directly on T-cells and suggest that alteration of cellular FA may be a worthwhile approach to control of inflammation.

8,11,14-Eicosatrienoic Acid↗
PubMed1986

The effects of perfluoro-n-decanoic acid in the rat heart.

Perfluoro-n-decanoic acid (PFDA) is a synthetic chemical resembling a 10-carbon fatty acid. Several studies have suggested that the toxic mechanism of PFDA may involve impaired lipid metabolism and/or altered cell membrane function. We examined the possibility that altered cell membrane structure in the heart might lead to changes in the functional activity of the organ. Functional characteristics were determined in the isolated perfused rat heart by measuring the ability of the heart to respond to either sympathetic nerve stimulation or infused norepinephrine. PFDA reduced the intrinsic resting heart rate and the inotropic response to a stimulus with maximal effects occurring 8 days after dosing. In addition, resting heart rate measured in vivo was found to be reduced in PFDA-treated rats 6 to 8 days after dosing. beta-Receptor binding studies conducted 8 days after a single dose of PFDA showed that the maximum binding capacity was reduced by PFDA treatment without significant changes in receptor affinity. It is concluded that the reduction in the inotropic response to catecholamines following PFDA treatment may be explained in part by lower beta-receptor density in the myocardial cell membrane. These effects may be related to the early fall in serum thyroid hormone levels as previously reported.

Animals↗
PubMed2006

Transcriptome profiling of Shewanella oneidensis gene expression following exposure to acidic and alkaline pH.

The molecular response of Shewanella oneidensis MR-1 to variations in extracellular pH was investigated based on genomewide gene expression profiling. Microarray analysis revealed that cells elicited both general and specific transcriptome responses when challenged with environmental acid (pH 4) or base (pH 10) conditions over a 60-min period. Global responses included the differential expression of genes functionally linked to amino acid metabolism, transcriptional regulation and signal transduction, transport, cell membrane structure, and oxidative stress protection. Response to acid stress included the elevated expression of genes encoding glycogen biosynthetic enzymes, phosphate transporters, and the RNA polymerase sigma-38 factor (rpoS), whereas the molecular response to alkaline pH was characterized by upregulation of nhaA and nhaR, which are predicted to encode an Na+/H+ antiporter and transcriptional activator, respectively, as well as sulfate transport and sulfur metabolism genes. Collectively, these results suggest that S. oneidensis modulates multiple transporters, cell envelope components, and pathways of amino acid consumption and central intermediary metabolism as part of its transcriptome response to changing external pH conditions.

Acids↗
PubMed2002

Delta6-, Stearoyl CoA-, and Delta5-desaturase enzymes are expressed in beta-cells and are altered by increases in exogenous PUFA concentrations.

In the evolution of Type II diabetes, an initial period of hyper-fatty acidemia leads to an insulin secretory defect which triggers overt hyperglycemia and frank diabetes. The mechanism by which elevated free fatty acids contribute to beta-cell dysfunction, however, is not clearly understood. We recently reported that arachidonic acid (20:4) or linoleic acid (18:2) supplementations result in increases in abundances of long chain polyunsaturated fatty acids in INS-1 beta-cell membrane lipids, suggesting that beta-cells express desaturases that catalyze generation of unsaturated fatty acids. As expression of desaturases by beta-cells has not yet been addressed, we initiated studies to examine this issue using INS-1 beta-cells and find that they express messages for the Delta6-, stearoyl CoA-, and Delta5-desaturase. Supplementation of the INS-1 beta-cells with arachidonic acid leads to decreased expression of all three desaturases, presumably in response to the decreased need for endogenous generation of unsaturated fatty acids. In contrast, linoleic acid supplementation promoted minimal changes in the three desaturases. These findings demonstrate for the first time that beta-cells express regulatable desaturases. Additionally, reverse transcriptase-polymerase chain reaction analyses reveal expression of the desaturases in native pancreatic islets. It might be speculated that long-term elevations in fatty acids can also adversely influence desaturase activity in beta-cells and affect PUFA composition in beta-cell membranes contributing to beta-cell membrane structural abnormalities and altered secretory function.

Animals↗
PubMed2005

Endothelium, a target for immune-mediated assault in connective tissue disease.

Evidence is lacking that antibodies (Ab) to endothelial cells (AECA) are pathogenic. They are frequently associated with antiphospholipid Ab (aPL), binding to complexes of phosphatidylserine (PS) with beta2GPI. Recent studies have, however, kindled a new debate on their pathogenicity of AECA. A group is responsible for PS reaching the surface of a cell, a feature of commitment to apoptosis. Defective clearance by macrophages of AECA-induced apoptotic cells might display beta2GPI on their surface, and challenge T cell tolerance, until aPL production. Some AECA are thus induced by cell membrane structures, while others recognize "planted" antigens and possibly ligand-receptor complexes. A second group promotes procoagulant factor, and a third has the capacity to trigger apoptosis. Clearly, the most direct demonstration of the pathogenicity of AECA is the autoAb-induced murine model of vasculiltis.

Antibodies, Antiphospholipid↗
PubMed1991

Conventional and high resolution scanning electron microscopy of biological sectioned material.

Intracellular structures of embedded biological tissues (rat kidney, myocardium and small intestine) were observed by conventional-scanning electron microscopy (C-SEM) and high-resolution scanning electron microscopy (HR-SEM) after glass knife sectioning. C-SEM of semi-thin sections of material processed the same way as conventional transmission electron microscopy (TEM) provided strong backscattered electron (BSE)-dependent, two-dimensional secondary electron images (SEI(-)) which precisely integrated and further extended previous light microscopy (LM) observation of the same specimen. In addition, the three-dimensional (3-D) arrangement of intracellular organelles was appreciated using a mixture of acetone-soluble acrylic resin in place of epoxy resin embedding. Since the identification of such structures was hampered by the use of conventional fixations we introduced osmium maceration as a preliminary step to remove excess cytoplasmic matrix from the specimen. Consequently, semi-thin sections for LM and thin sections for TEM were obtained by sectioning of the tissue blocks. After resin removal, the sections were successfully observed in 3-D under a C-SEM. Finally, the deembedded, osmium treated sections proved to be smooth enough to facilitate deposition of continuous, ultra-thin (1 nm) chromium films and, therefore, HR-SEM studies of macromolecular cell membrane structures.

Animals↗
PubMed1978

Promotion of radiation peroxidation in models of lipid membranes by caesium and rubidium counter-ions: micellar linoleic and linolenic acids.

Caesium and rubidium counter-ions increase peroxidation in irradiated micelles of linoleic (18 : 2) and linolenic (18 : 3) acids. The effect is specific to Cs+ and Rb+ in the alkali metal series. The effect is independent of the salts used (Cl-, NO3-, ClO4-) and, therefore, independent of the chaotropic nature, and reactivity with hydroxyl radicals of Cl-, NO3- and ClO4-. The promotion of peroxidation by Cs+ and Rb+ is interpreted in terms of their effect on fatty acid micelle structure. The dependence of radiation peroxidation on lipid structure in the micelles may be significant for studies of peroxidation in highly structured cell membranes.

Cesium↗
PubMedDate not supplied

Analysis of membrane fluidity alterations and lipid disorders in type I diabetic children and adolescents.

The degree of random orientation of excited diphenylhexatriene molecules in isolated erythrocyte membrane ghosts was investigated in order to determine the possible effect of lipid disorders on membrane structure in children suffering from type I diabetes mellitus with and without diabetic retinopathic lesions. A decrease of cholesterol in the antiatherogenic fraction HDL (1.17 +/- 0.06 in retinopathy vs 1.24 +/- 0.065 in controls) and its increase in atherogenic LDL fraction (3.88 +/- 0.23 vs 2.63 +/- 0.26) as well as developing erythrocyte membrane rigidization in diabetes and retinopathy (0.193 +/- 0.008 and 0.204 +/- 0.014 vs 0.161 +/- 0.008 in controls) were observed. Considerable fluctuations in plasma and membrane cholesterol:phospholipid ratio were most pronounced in subjects exhibiting diabetic background retinopathy. The content of membrane cholesterol compared significantly with both membrane fluidity (r = 0.677), cholesterol of LDL (r = 0.667) and cholesterol:phospholipid ratio in HDL (r = 0.693) which suggests a destructive effect of lipid disorders on cell membrane structure in diabetics.

Adolescent↗
PubMed1996

The rate of transbilayer movement of erythrocyte membrane cholesterol is correlated with sodium-lithium countertransport.

Hypertension is associated with some abnormalities in cell membrane structure, including an impaired distribution of cholesterol into the monolayers of erythrocyte membrane. Transbilayer movement of membrane cholesterol modulates the formation of these structural cholesterol domains. We tested whether the rate of cholesterol movement may influence on the erythrocyte Na(+)-Li+ countertransport, that is a marker of human essential hypertension. In single regression analysis, the half-time for the decrease in specific radioactivity of cholestenone (inverse of membrane cholesterol transbilayer movement) was negatively related to the erythrocyte cation flux mediated by Na(+)-Li+ countertransport (r = -0.8983, P < 0.0001 for control subjects; r = -0.8191, P < 0.005 for normocholesterolaemic hypertensive patients; r = -0.7664, P < 0.005 for hypercholesterolaemic hypertensive patients). These data suggest that changes in the transbilayer movement of membrane cholesterol interfere with the main cation transport system which is implicated in the pathophysiology of essential hypertension. This also provides a new link between kinetic cholesterol pools and cell membrane functions.

Antiporters↗
PubMed1986

Monitoring of effects of cis-diamminedichloroplatinum (II). Part III. Effect of platinum complexes on PHA-stimulated proliferation of human peripheral blood mononuclear cells in vitro.

The effect of the platinum complexes cis-DDP and CBDCA on the functions of human peripheral blood mononuclear cells (PBMC)--viability, proliferating activity after polyclonal stimulation with phytohemagglutinin is followed in an in vitro study. Both the platinum complexes (at concentrations 10(-5) up to 10(-9) mol/l) inhibit significantly the proliferating activity of PBMC without affecting its viability, i.e. integrity and permeability of the cell membrane structures. As to effectivity, cis-DDP has shown itself a more effective inhibitor of cellular proliferation than CBDCA of which 10-100 times higher concentrations are required to achieve the same inhibitory effect in dependence on the temporal relation to the application of phytohemagglutinin. The highest inhibitory effect is noted when cis-DDP is applied either simultaneously with, or 48 h after PHA, i.e. at the stage of maximum proliferating activity. The results bring support to the assumed mechanism of action of the above platinum complexes--intervention into DNA synthesis. Since the test of blastic transformation of PBMC is held to be an image primarily of the function of T lymphocytes, it may be inferred that platinum cytostatics can affect cell-mediated immunity also in patients.

Adult↗
PubMedDate not supplied

Effect of Ca2+ on structure and fluidity of microvillus membranes of human placenta.

This investigation shows the effect of a Ca2+ addition on the structural and physiochemical properties of microvillus plasma membranes obtained from human placenta. Ca2+ addition induces an increase in microviscosity, as shown by the increase of order parameter and rotational correlation time of 5- and 16-doxylsterate derivatives and by the increase of fluorescence polarization of diphenylhexatriene. All the effects were obtained in a wide temperature range. The morphometric analysis of the ultrastructural images shows that the vesicle profiles of syncytiotrophoblast membranes decrease both area and form factor (FF) in the presence of Ca2+ with respect to the controls. The freeze-fracture results also show that Ca2+ induces an enhanced tendency to IMP clusterization. The Ca2+-induced changes were observed in both E and P faces. Our results underline the important role of Ca2+ in the cell membrane structure per se and in modulating interactions between cytoplasmic and extracellular microenvironments. The results of morphometric analysis of the ultrastructural images agree with biochemical data showing an increased stability induced by calcium on plasma membranes.

Calcium↗
PubMed1981

Properties of cell membranes relevant to anaesthesiology.

Recent advances in the study of cell membrane structure and function confirm the Singer-Nicolson model of a lipid bilayer in which membrane proteins are embedded. Mobility of these proteins is essential for biological activity. The Ca2+-ATPase of skeletal muscle is a typical example of a transmembrane integral protein. Within this protein various domains can be identified on the basis of their functional activities. A hydrophobic pocket within the APTase polypeptide appears to be a possible site of interaction with halothane molecules. These findings may explain the well-known correlation between anaesthetic potency and lipid solubility with specific inhibition of functions known to be mediated by membrane proteins.

Anesthesia↗
PubMed2004

Phosphatidylinositol-4,5-bisphosphate-rich plasma membrane patches organize active zones of endocytosis and ruffling in cultured adipocytes.

A major regulator of endocytosis and cortical F-actin is thought to be phosphatidylinositol-4,5-bisphosphate [PtdIns(4,5)P2] present in plasma membranes. Here we report that in 3T3-L1 adipocytes, clathrin-coated membrane retrieval and dense concentrations of polymerized actin occur in restricted zones of high endocytic activity. Ultrafast-acquisition and superresolution deconvolution microscopy of cultured adipocytes expressing an enhanced green fluorescent protein- or enhanced cyan fluorescent protein (ECFP)-tagged phospholipase Cdelta1 (PLCdelta1) pleckstrin homology (PH) domain reveals that these zones spatially coincide with large-scale PtdIns(4,5)P2-rich plasma membrane patches (PRMPs). PRMPs exhibit lateral dimensions exceeding several micrometers, are relatively stationary, and display extensive local membrane folding that concentrates PtdIns(4,5)P2 in three-dimensional space. In addition, a higher concentration of PtdIns(4,5)P2 in the membranes of PRMPs than in other regions of the plasma membrane can be detected by quantitative fluorescence microscopy. Vesicular structures containing both clathrin heavy chains and PtdIns(4,5)P2 are revealed immediately beneath PRMPs, as is dense F actin. Blockade of PtdIns(4,5)P2 function in PRMPs by high expression of the ECFP-tagged PLCdelta1 PH domain inhibits transferrin endocytosis and reduces the abundance of cortical F-actin. Membrane ruffles induced by the expression of unconventional myosin 1c were also found to localize at PRMPs. These results are consistent with the hypothesis that PRMPs organize active PtdIns(4,5)P2 signaling zones in the adipocyte plasma membrane that in turn control regulators of endocytosis, actin dynamics, and membrane ruffling.

3T3 Cells↗
PubMed2006

[Omega 3: is there a situation of deficiency in young children?].

This paper starts with a review of the metabolism of n-6 (omega6) and n-3 (omega3) fatty acids, the resulting eicosanoids (prostaglandins, leucotrienes, and thromboxanes), and the physiological functions they are involved in, with special emphasis on effects during pregnancy (such as possible benefits on fetal growth, prevention of hypertension of pregnancy, and prevention of premature labor). Attention is then turned to the key role for long-chain polyunsaturated fatty acids (LCPUFAs), most notably docosahexaenoic acid (DHA), in central nervous system and retinal cell membrane structure and in cerebral and retinal development. Massive maternofetal transfer of LCPUFAs occurs during the third trimester of pregnancy, so that maintaining an adequate intake of DHA during pregnancy is crucial. Preterm babies must receive sufficient amounts of DHA, either via breast milk or via formula supplemented with LCPUFAs, both of which prevent DHA levels from declining in blood and cerebral phospholipids. These two methods of achieving an adequate DHA intake ensure normal maturation of visual acuity and cognitive function, as shown by randomized controlled trials. Formula supplemented with fish oils rich in n-3 LCPUFAs but lacking a proportionate supply of arachidonic acid (ArA, 20: 4n-6) negatively affects somatic growth, confirming the need for an adequate ArA supply. Eicosapentaenoic acid (EPA) can also exert negative effects. Therefore, the best source of supplemental LCPUFAs may be oil from single-cell algae and microscopic fungi, which contains adequate amounts of DHA and ArA. In full term neonates, strong arguments support LCPUFA supplementation, despite continuing controversy generated by conflicting results from interventional studies. These discrepancies in study results may be ascribable to differences in study design, patient age, intervention duration, assessment tool sensitivity, and LCPUFA sources. In 1996, an amendment to the European Directive on infant formulas and follow-on formulas was developed to authorize LCPUFA supplementation and to specify appropriate ranges. As a result, formulas supplemented with DHA and ArA were introduced on the market. Pregnant and nursing women should be advised to maintain an adequate dietary intake of DHA in order to meet their increased needs and those of the fetus or infant.

Animals↗
PubMed1989

[Involvement of lipid peroxidation in regression of heart hypertrophy].

The regression of hypertrophied heart presupposes disassembling of all cardiomyocyte components including membrane structures. The involvement of free radical oxidation of membrane phospholipids was studied in the cardiac regression. Altitude hypertrophy was developed in barocamera (7000 m, 6 hours daily). 3 weeks of periodical hypoxia leads to 1.5-fold increase of heart weight (right ventricle weight was 2-fold increased). In 7-10 days after adaptation the heart weight reduced to normal. Both, the development and regression of myocardial hypertrophy was accompanied by changes in Mb and Hb organ concentration proportional to weight changes. In lipid extraction of maximal hypertrophied heart, the 30% decrease of lipid peroxidation product (diene conjugates) regularly occurred. The rate of regression had negative correlation with peroxidation products accumulation. Intraperitoneal injection of free radical scavenger BHT attenuate the regression rate. The results suggest that unlike the common knowledge about the membrane injury effect, lipid peroxidation can play positive role in disassembling of superfluous cell membrane structures.

Animals↗
PubMed2002

The myotoxicity of statins.

PURPOSE OF REVIEW: Since hypercholesterolaemia is a chronic condition, the long-term safety of statins is important. Adverse reactions involving skeletal muscle are the most common (reported incidence 1-7%). The recent withdrawal of cerivastatin because of deaths from rhabdomyolysis, of which 25% were related to gemfibrozil-cerivastatin combination therapy, has focused attention on myotoxicity associated with statins and in particular with statin-fibrate combinations. We review the safety profiles of the individual statins, and discuss the mechanisms that may account for myotoxicity associated with statins and these agents and how these may relate to the different myotoxic potential of individual agents. RECENT FINDINGS: The statins, particularly the first-generation agents, have been well evaluated from the perspective of safety and efficacy. Cerivastatin was associated with a 10-fold higher incidence of myotoxicity than any other statin, suggesting that there may be differences in myotoxic potential between agents. Statin-associated myotoxicity is complex, involving effects on cell membrane structure and function, mitochondrial dysfunction and impaired myocyte duplication. Potential differences in myotoxicity between agents may relate to the physicochemical, pharmacokinetic and pharmacodynamic properties of individual drugs. The aetiology of myotoxicity associated with statin-fibrate combination therapy is complex and multifactorial, with recent studies suggesting that there may be differences in myotoxic potential between individual fibrates. SUMMARY: Recent evidence suggests that there may be differences in myotoxic potential between individual agents. Thus, the choice of hypolipidaemic therapy needs to be based not only on outcome evidence and cost-effectiveness analysis, but also on safety considerations for individual agents.

Anticholesteremic Agents↗