influence of lipid composition and beta-carotene on lipid peroxidation in liposomes

Oxidative damage to membrane lipid is one of the prime events occurring in aging and other undesirable physiological processes. In this study experiments were performed on liposomes [prepared either from crude erythrocyte phospholipids or purified egg yolk phosphatidylcholine] as models of lipid bilayer portion of biomembranes. The effects of beta-carotene, and phospholipid composition on peroxidation process, initiated by Fe[2+], were studied. It was found that beta-carotene does not show any noticeable antioxidant effect on the peroxidation process initiated by Fe[2+] in liposomes prepared from erythrocyte phosphatides, whereas it effectively suppressed the same process in egg yolk phosphatidylcholine [EYPC]. It is concluded that the anti-/pro-oxidant activity of beta-carotene is also dependent on the membrane lipid composition and this may provide an explanation about the conflicting reports on its role in ordinary or promoted oxidation experiments

Carbohydrate induced modulation of cell membrane. IV: Interaction with mucin and fucoidan totally immobilizes the human platelet membrane.

P selectins and E selectins are cell adhesion molecules that mediate the interaction of platelets and endothelial cells with neutrophils and monocytes. The proposed ligands for these receptors contain the Le(x) core, sialic acid and sulfated fucose. In this paper we report that binding of sialic acid markedly restricts the mobility of membrane proteins and lipids as studied by EPR spectroscopy using spin probes. Binding of mucin and fucoidan totally restricts the mobility probably due to cross-linking of the surface lectins. Binding of these ligands also resulted in an increase in the cytoplasmic viscosity.

Molecular and physicochemical aspects of local anesthetic-membrane interaction

Local anesthesia is achieved by the binding of anesthetic molecules to the sodium channel, a membrane protein responsible for the transport of the extracellular sodium to the cytosol. Local anesthetics (LA) bind to the sodium channel inhibiting sodium transport and, as a consequence, the action potential responsible for the nervous impulse. Most LA are relatively hydrophobic ionizable amines that undergo partitioning into lipid. Both activity and toxicity correlate positively with LA hydrophobicity. Effects of LA on the structural and dynamical properties of the membranes lipid region may be responsible for some of the toxic effects caused by these molecules. The present review focuses on research done on the interaction between both the charged and uncharged forms of LA and lipid systems - bilayers and micelles. LA have been found to alter phospholipid gel to liquid crystal phase transition temperature (Tc), to affect bilayer permeability, to influence molecular packing, and to inhibit the bilayer to hexagonal phase transition. Anesthetics in micellized form disrupt bilayers giving rise to lipid-LA mixed micelle-like aggregates. The question of LA location in the bilayer is also addressed. Special emphasis is placed on work focusing on the quantitative analysis of drug binding, as well as on the effects of binding on physicochemical properties of the LA, such as extent of ionization (pK shifts) and rates of chemical reactions. The understanding of these phenomena has contributed to the development of less toxic liposomal formulations capable of prolonging the duration of anesthesia.

Developmentally-regulated cell surface N-linked oligosaccharides participate in intercellular cohesion in Dictyostelium discoideum.

The ability of purified plasma membrane glycoconjugates to inhibit the EDTA-resistant agglutination between aggregation-stage cells of Dictyostelium discoideum has suggested that receptor binding of these glycoconjugates provides a basis for cell-cell cohesion during aggregation. This has been tested by analysis of a series of mutants with different defects in the assembly of N-linked oligosaccharides. Mutant HL241 lacks outer branch components of N-linked oligosaccharides and fails to aggregate or express EDTA-resistant cohesion. HL244 makes unsulphated but otherwise normal N-linked oligosaccharides, generates multiple tips on aggregated cell mounds in some clones, and shows abnormally strong EDTA-resistant cohesion. Two mutants that are temperature-sensitive for complete processing of N-linked oligosaccharides are also temperature-sensitive for expression of both aggregation ability and EDTA-resistant cohesion. A revertant that recovered essentially normal N-linked oligosaccharide processing at the restrictive temperature has also recovered its ability to aggregate and to agglutinate in EDTA.

Lipid molecular shapes and membrane architecture.

A simple biomembrane like erythrocyte contains well over hundred lipid species with diverse molecular shapes differing in the number of acyl chains, chain length, unsaturation and head group composition. A delicate balance between these molecular shapes is necessary in order to have a functional membrane. It is well established that the activities of a number of membrane-bound enzymes and other properties such as aggregation, spontaneous vesiculation, pathophysiological properties and lipid-protein interactions of lipids depend on the acyl chain length, unsaturation and head group composition. In fact, the molecular shape of a phospholipid molecule, as modulated by changes in chain length, unsaturation and head group composition, is probably what is affecting the above mentioned properties. The molecular shape of a lipid depends on a dimensionless packing parameter, S, the value of which influences the size and shape of aggregate formed upon hydration. In fact, the additivity of S values of lipid mixtures explains a number of experimental observations. The molecular shape concept, although very simple, explains many membrane phenomena like complementarity of molecular shapes of non-bilayer lipids to form stable bilayers. Membrane permeability is controlled to a large extent by lipid packing which depends upon molecular shapes. In fact, membranes maintain their lamellar structure by delicately balancing the composition of bilayer-forming and non-bilayer-forming lipids indicating that complementarity of molecular shapes is essential to maintain the permeability barrier. Based on this, the complementary molecular shape model of cell membrane is proposed.

How do peptides interact with lipid membranes and how does this affect their biological activity?

1. A short review is given of the chemical, physical, and pharmacological development of the idea that target cell lipid membranes may catalyze the interaction between regulatory peptides (or other pharmacologic agents) and their cell surface receptors. 2. The message-address and the membrane compartments concepts explain the observed correlations between the three-dimensional structures of peptides induced by a membrane surface and their preference for a certain receptor subtype. 3. Examples are given for opioid peptides (enkephalin, dynorphin, etc.), tachykinin peptides (substance P, neurokinin A, etc.), and melanocortin peptides (ACTH, alpha-MSH, etc.). 4. Relationships between the conformation of substance P induced by membrane association and that of a non-peptide substance P mimetic are discussed. Possible reasons for the difference between agonistic and antagonistic properties in the peptide field are revealed by this case

Polyene antibiotics in the membrane environment.

The cytotoxic activity of the polyene antibiotics mainly depends on the appearance of the drug species which arises from drug-sterol complexation. The unsaturation and intact macrolide ring of the polyenes are the requirements for the biological activity. All the polyene antibiotics can form the complex with the sterol having 3 beta-OH group, and planar ring and a hydrophobic side chain. Aromatic polyene antibiotics with positively charged head group have been considered as most potential antifungal agents.

Glycolipid composition of a mutant cell line of mouse FM3A cells, and the effect of exogenous glycolipids on cell growth.

Had-1 isolated from mouse mammary tumour FM3A cells as a non-permissive cell line to Newcastle disease virus infection is deficient in NDV receptors, and galactosylation of the complex type sugar chains of the glycoproteins is extensively reduced compared to FM3A cells. It is also deficient in UDP-galactose transport into Golgi vesicles. The major neutral glycolipids in FM3A is Lac-Cer, whereas, in Had-1 cell, Glc-Cer is the major glycolipid and the concentration of neutral glycolipids is one-tenth as low as that in FM3A. GM3, GD3 and sialyl i- and I-type lactosaminylceramide are the gangliosides present in both FM3A and Had-1, although their presence in both cells is only in traces. Had-1 contains relatively high N-glycolyl-neuraminic acid. Among the several glycolipids tested, Lac-Cer, Gg-4-Cer and Glc-Cer showed inhibitory effect on proliferation of Had-1 cells, but did not show any appreciable effect on that of FM3A cells. Lac-Cer had the most potent inhibitory effect and this inhibitory effect was completely reversible. While mice injected with 5 x 10(6) cells of FM3A died in one month, those injected of Had-1 cells at the same dose survived for more than 6 months. Thus glycolipids on the cell surface play an essential role during cell growth both in vivo and in vitro.