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Biomedical subjects

M Shinitzky

Publications and source records attributed to M Shinitzky.

At least 73 records · Page 4Linked to original sources
PubMed1982

Alleviation of drug withdrawal symptoms by treatment with a potent mixture of natural lipids.

Acute treatment with morphine, as well as with other addictives, causes an initial decrease in brain membrane lipid microviscosity. Upon chronic exposure to the addictive drug, the original fluidity of brain membranes is restored, mostly due to an increase in the cholesterol content. Withdrawal of the drug leaves the membranes hyperviscous and the central nervous system supersensitive, as manifested in the abstinence syndrome. Based on this scheme of events, we have designed treatments of addicted mice with a special lipid mixture extracted from hen egg-yolk (Active-lipid, AL), which is a highly potent membrane fluidizer. In vivo treatment of morphine-addicted mice with AL, either by injection or as a diet supplement, reversed the brain membrane hyperviscosity and, concomitantly, markedly reduced, or even completely abolished the withdrawal symptoms precipitated by naloxone. Treatments with the fully saturated, rigidifying phospholipid dipalmitoyl-lecithin, exacerbated the withdrawal symptoms. These results could be the basis for a novel innocuous treatment which may facilitate the rehabilitation of drug and alcohol addicts.

Animals↗
PubMed1982

Resolution of plasma membrane lipid fluidity in intact cells labelled with diphenylhexatriene.

The partitioning of fluorescence probes into intracellular organelles poses a major problem when fluorescence methods are applied to evaluate the fluidity properties of cell plasma membranes with intact cells. This work describes a method for resolution of fluidity parameters of the plasma membrane in intact cells labelled with the fluorescence polarization probe 1,6-diphenyl-1,3,5-hexatriene (DPH). The method is based on selective quenching, by nonradiative energy transfer, of the fluorescence emitted from the plasma membrane after tagging the cell with a suitable membrane impermeable electron acceptor. Such selective quenching is obtained by chemical binding of 2,4,6-trinitrobenzene sulfonate (TNBS), or by incorporation of N-bixinoyl glucosamine (BGA) to DPH-labelled cells. The procedures for determination of lipid fluidity in plasma membranes of intact cells by this method are simple and straightforward.

Animals↗
PubMed1982

Increase in lipid microviscosity of unilamellar vesicles upon the creation of transmembrane potential.

Diffusion potential of potassium ions was found in unilamellar vesicles of phosphatidyl choline. The vesicles, which included potassium sulfate buffered with potassium phosphate were diluted into an analogous salt solution made of sodium sulfate and sodium phosphate. The diffusion potential was created by the addition of the potassium-ionophore, valinomycin. The change in lipid microviscosity, ensuing the formation of membrane potential, was measured by the conventional method of fluorescence depolarization with 1,6-diphenyl-1,3,5-hexatriene as a probe. Lipid microviscosity was found to increase with membrane potential in a nonlinear manner, irrespective of the potential direction. Two tentative interpretations are proposed for this observation. The first assumes that the membrane potential imposes an energy barrier on the lipid flow which can be treated in terms of Boltzmann-distribution. The other interpretation assumes a decrease in lipid-free volume due to the pressure induced by the electrical potential. Since increase in lipid viscosity can reduce lateral and rotational motions, as well as increase exposure of functional membrane proteins, physiological effects induced by transmembrane potential could be associated with such dynamic changes.

Liposomes↗
PubMed1982

Senescence and the Fluidity of Rose Petal Membranes : RELATIONSHIP TO PHOSPHOLIPID METABOLISM.

In previous work, senescence of rose petal cells has been shown to be accompanied by a gradual decrease of membrane fluidity, as measured by a fluorescence polarization technique. Concomitantly, an increase in the free sterol-to-phospholipid ratio was found. Both observations were verified in this study. Further, experiments carried out on whole tissue and isolated protoplasts during senescence revealed that there was no quantitative change in the level of free sterols. The content of phospholipids decreased without any significant change in their composition. Results from experiments measuring the incorporation of [(32)P]orthophosphate indicated a reduced capacity for phospholipid synthesis in senescent cells. Both young and old tissue showed phospholipase A and D activity, the former increasing with age.It was concluded that the fluidity of rose petal membranes decreases with age as a result of a decrease in phospholipid content, brought about by both reduced synthesis and enhanced degradation. Evidence supporting the view that the phenomena observed are related specifically to changes in the plasmalemma is discussed.

Journal Article↗
PubMed1982

Acceleration of membrane senescence in cut carnation flowers by treatment with ethylene.

The lipid microviscosity of microsomal membranes from senescing cut carnation (Dianthus caryophyllus L. cv. White Sim) flowers rises with advancing senescence. The increase in membrane microviscosity is initiated within 3 to 4 days of cutting the flowers and coincides temporally with petal-inrolling denoting the climacteric-like rise in ethylene production. Treatment of young cut flowers with aminoethoxyvinylglycine prevented the appearance of petal-inrolling and delayed the rise in membrane microviscosity until day 9 after cutting. When freshly cut flowers or aminoethoxyvinylglycine-treated flowers were exposed to exogenous ethylene (1 microliter per liter), the microviscosity of microsomal membranes rose sharply within 24 hours, and inrolling of petals was clearly evident. Thus, treatment with ethylene accelerates membrane rigidification. Silver thiosulphate, a potent anti-ethylene agent, delayed the rise in microsomal membrane microviscosity even when the flowers were exposed to exogenous ethylene. Membrane rigidification in both naturally senescing and ethylene-treated flowers was accompanied by an increased sterol:phospholipid ratio reflecting the selective loss of membrane phospholipid that accompanies senescence. The results collectively indicate that the climacteric-like surge in ethylene production during senescence of carnation flowers facilitates physical changes in membrane lipids that presumably lead to loss of membrane function.

Journal Article↗
PubMed1982

Modulation of complement lysis of human erythrocytes by the membrane lipid viscosity.

Human red blood cells (H-RBC), sensitized by specific rabbit antihuman hemolysin, showed a significant increase in susceptibility to complement lysis after rigidification of the membrane lipid layer by incorporation of cholesterol (p less than 0.001). Conversely, fluidization of the membrane lipid layer by treatment with phosphatidylcholine for cholesterol depletion displayed increased tolerance to the complement lysis (p less than 0.01). Antisera, obtained from 6 rabbits immunized with untreated H-RBC, were tested separately. The average serum concentration, exerting 50% hemolysis, was 1,1 +/- 0.4% for the cholesterol-enriched H-RBC and 16.3 +/- 7.5% for cholesterol-depleted H-RBC.

Animals↗
PubMed1981

Glucose transport through cell membranes of modified lipid fluidity.

Carrier-mediated transport of glucose in human erythrocytes and 3T3 mouse fibroblasts was examined at different lipid viscosities of the cell membrane. Rigidification of the membrane lipid layer was accomplished by incorporation of cholesterol or one of the hydrophilic esters, cholesteryl hemisuccinate or cholesteryl betainate, whereas fluidization was accomplished by cholesterol depletion. In both cells the dependence of the maximal rate of glucose transport at 37 degrees C, Vmax, on the lipid microviscosity of the cell plasma membrane, eta, is of a similar pattern which does not obey simple diffusion considerations. When the eta value of untreated cells is slightly increased (10-20%), Vmax increases to a peak value, beyond which a further increase in eta progressively reduces it. Decrease of the natural eta is also accompanied by a progressive decrease of Vmax. This general pattern was also observed for the transport of alpha-aminoisobutyric acid in 3T3 fibroblasts (unpublished results). A theoretical analysis of the dependence on eta of the transport turnover number and of the accessibility of carrier sites was carried out in order to account for this behavior. On the basis of this analysis, a general expression for the dependence of Vmax on eta, which fits reasonably well with the experimental data, was derived. This expression is also valid for the dependence on eta of the overt activity of membrane-bound enzymes and receptors.

Animals↗
PubMed1981

Lipid-induced modulation of opiate receptors in mouse brain membranes.

The binding of [3H] D-Ala-enkephalinamide (DAEA) to crude mitochondrial fractions (P2M) from mouse forebrain was determined after modulation of membrane lipid microviscosity. Lipid fluidization of P2M membranes, following treatment with egg lecithin, resulted in a 50% loss of specific binding of DAEA. Increasing the P2M lipid microviscosity, by incorporation of cholesteryl hemisuccinate (CHS), increased the accessibility of the opiate receptors up to a peak level of 170% which decreased sharply upon further increase in lipid microviscosity. The processes resulting from lipid rigidification may have important implications for aging and for drug addiction.

Animals↗
PubMed1981

Elevation of apparent membrane viscosity in ovarian granulosa cells by follicle-stimulating hormone.

Continued exposure of cultured granulosa cells to follicle-stimulating hormone (FSH) induced: (i) a rise in apparent membrane microviscosity, as reflected by an increase in fluorescence polarization of the lipid-soluble probe, 1,6-diphenyl-1,3,5,-hexatriene; and (ii) a progressive decline in the cyclic AMP response to renewed challenge with the same hormone. Both changes were reduced or prevented by pretreatment of the cells with oleic or linoleic acid, agents which reduce membrane viscosity, but not by elaidic or palmitic acid which increase the rigidity of membrane lipids. Other agents that inhibited FSH-induced changes in membrane fluidity (gonadotropin-releasing hormone, actinomycin D and cycloheximide) also prevented desensitization to FSH. Cyclic AMP and cyclic GMP derivatives did not mimic the effects of FSH on apparent membrane viscosity or desensitization. Changes in membrane fluidity are unlikely to be the sole cause of desensitization since (i) pretreatment of the cells with fatty acids that increase lipid viscosity did not induce desensitization to FSH, and (ii) desensitization of granulosa cells to lutropin and prostaglandin E2 by exposure to the homologous hormone was not attended by increased membrane viscosity. The experiments described provide the first example of a hormonally induced increase in the target cell apparent membrane viscosity.

Animals↗
PubMed1981

Plasma membrane microviscosity of Lewis lung carcinoma cells derived from local growth and pulmonary metastases.

Significant differences in plasma membrane microviscosity between 3LL Lewis lung carcinoma cells, grown at the site of their original inoculation (1-3LL), and the pulmonary metastatic cells of this tumor (m-3LL) were detected by a recent improvement of the fluorescence polarization technique, especially designed for cells in suspension. Membrane microviscosity was also found to depend on the site of the growth and the stage of tumor development. The results show that lung metastases are lower in membrane microviscosity compared to 1-3LL and that, within the latter, cells grown in the muscle are characterized by higher microviscosity than those grown under the skin or in the footpad. Within one transplantation period, 3LL tumor cells tend to acquire membrane microviscosity values typical of the anatomical location of tumor growth. Tumors at advanced stages were generally found to be more rigid than young ones, where tumor size (volume) rather than its age seemed to determine the membrane microviscosity. These differences are discussed in terms of both the causes and the biological, as well as immunological, implications in relation to the newly proposed hypothesis of passive modulation of antigenic expression.

Animals↗
PubMed1980

pH-sensitive liposomes: possible clinical implications.

When pH-sensitive molecules are incorporated into liposomes, drugs can be specifically released from these vesicles by a change of pH in the ambient serum. Liposomes containing the pH-sensitive lipid palmitoyl homocysteine (PHC) were constructed so that the greatest pH differential (6.0 to 7.4) of drug release was obtained near physiological temperature. Such liposomes could be useful clinically if they enable drugs to be targeted to areas of the body in which pH is less than physiological, such as primary tumors and metastases or sites of inflammation and infection.

Antineoplastic Agents↗
PubMed1980

Induced drug release from lipid vesicles in serum by pH-change.

Drugs can be released from lipid vesicles by pH-change in calf, horse or human serum when pH-sensitive trigger molecules are incorporated in the vesicle lipid bilayer. The lipid composition is so chosen that the drug release is best performed at 37 degrees C. Specific drug targeting is envisaged to loci of the body with lower than physiological pH, such as primary or metastatic tumors.

Animals↗
PubMed1980

Correlation between cell density, membrane fluidity, and the availability of transferrin receptors in Friend erythroleukemic cells.

Undifferentiated Friend erythroleukemic cells (FL-cells) acquire membrane microviscosity (eta), in accord with the culture cell density. At low cell density eta (21 degrees) approximately 2.8 poise, whereas at confluency it increases to eta (21 degrees) approximately 5.3 poise. Concomitantly, the total number of available transferring receptors per cell decreases by about 80% upon increase in cell density. Modulation of membrane microviscosity, by artificial alteration of the membrane cholesterol level, mediates similar modulations of the availability of the transferrin receptors. The correlation between the availability of the transferring receptors and the membrane lipid fluidity may take part in the overt decrease in iron uptake by erythroid cells along the erythropoiesis pathway.

Animals↗