Mammalian cell membranes

The presence and biological importance of oligosaccharide structures, usually as components of glycolipids and glycoproteins, in bacterial capsular and cell-wall polysaccharides, in mammalian cell membranes, in cytoplasm, and in extracellular fluids, are now well documented. They are important constituents in... 

Effector-induced SMase activation plays a highly pivotal role in apoptosis signaling since it has been described that the absence of CER generation, due to a defect in SMase stimulation, leads to cell resistance (for review see Eevade and Jaffrezou, 1999). However, the spacio-temporal organizahon of these events is unclear. SM, a major constituent of mammalian cell membranes, is found essentially within the plasma membrane and concentrated mostly in its outer leaflet. However, we and others have demonstrated that in response to cytotoxic effectors such as... 

This reduction in self-aggregated AmB and the stability of the formulation suggested that LC-AmB could be a useful pharmaceutical formulation because it is generally accepted that the origin of toxicity toward mammalian cell membranes is free, self-associated AmB (2). 

The discovery of penicillin and its successful application in World War II inspired the antibiotic era, and a broad search for other cures for infectious diseases. Cancer has a totally different cause, as it arises through the malignant mutation of normal cells instead of from the actions of bacterial or other outside organisms. Penicillin destroys the bacteria cell walls, but not the mammalian cell membranes. Unless a dmg could be found that could tell the difference between a normal cell and a cancer cell, then it was not clear that there would be an effective cancer drug, that is until the first report by Goodman in 1946 that nitrogen mustard, developed as a war gas, was an effective chemotherapeutic for human leukemia. 

Another method employed to minimize fouling is the use of phospholipid coating designed to mimic the normal mammalian cell membrane. The best studied of these compounds has been phosphorylcholine (PC). For example, Goreish et al. applied PC to polyethylene terephthalate substrate and found that PC decreased the number of inflammatory cells that bound to the substrate.79 More important, they also implanted PC-coated substrates intramuscularly in rabbits and found that at week 13, the encapsulation tissue as a result of the foreign body reaction was much thinner in the PC-treated tissue samples. 

The negatively charged phospholipid phosphatidylserine is asymmetrically distributed in mammalian cell membranes, primarily on the inner leaflet. Upon exposure to collagen or thrombin, the distribution of phospholipids changes with increasing phosphatidylserine in the external membrane leaf (I). The increased expression of phosphatidylserine on the outer leaflet of the membrane creates a procoagulant surface on which several steps of the coagulation cascade take place. 

Wisden W, Parker EM, Mahle CD, et al. Cloning and characterization of the rat 5-HT5B receptor. Evidence that the 5-HT5B receptor couples to a G protein in mammalian cell membranes. FEBS Lett 1993 333 25-31. 

Stubbs, C.D. and Smith, A.D., The modification of mammalian cell membrane polyunsaturated fatty acid composition in relation to membrane fluidity and function, Biochim. Biophys. Acta, 779, 89, 1984. 

Unfortunately, there are few pure examples of true selective toxicity. Perhaps the best is penicillin. The therapeutic specificity of this antibiotic is based upon the qualitative difference between bacterial cell wall synthesis and mammalian cell membrane synthesis. Synthesis of the former can be inhibited by penicillin while the latter is unaffected. Thus, penicillin is one of the few examples of a drug that can actually cure an illness. A similar example involves the sulfa drugs, which interfere with the synthesis of folic acid, used in nucleic acid formation, in bacteria. While bacteria must synthesize their own folic acid, mammalian cells utilize dietary, preformed folic acid and are not susceptible to interference with its formation. 

Microbes also have a plasma membrane that resides adjacent to their cell wall. Polymyxins are amphipathic agents (containing both nonpolar, lipophilic and polar, lipophobic groups) that interact with phospholipids in microbial cell membranes. The result is disruption of the membrane and increased permeability. However, because microbial and mammalian cell membranes are not exceedingly dissimilar, polymixins can produce significant toxicity in humans (i.e., they have low selective toxicity). This is also true for the related drug nystatin. This is why these particular antibiotics are not generally used systemically and are usually restricted to topical application. 

While the main thrust of this book remains centered on the phosphorus-containing lipids of mammalian cell membrane, it would be remiss on the author s part not to discuss the sphingogiycolipids. These phosphorus-free, sphingosine-containing lipids coexist with the phospholipids in cellular membranes. In place of a phosphocholine moiety (as in sphingomyelin), a carbohydrate is substituted. These complex lipids were found to be present in significant amounts in brain some 60 years ago, and their potential association with... 

Mammalian cell membranes consists of a variety of lipids. The phospholipids, phosphatidylcholine (PC) and phosphatidylethanolamine (PE) are quantitatively the most important lipids in cellular membranes. PC and PE are synthesized via different pathways in mammalian cells. 

Lipids account for about 40% of the total mass of the typical mammalian cell membrane. One class of lipids, the sterols, acts as the precursor to steroid... 

Lykidis A and Jackowski S (2001) Regulation of mammalian cell membrane biosynthesis. Progress in Nucleic Acid Research and Molecular Biology 65,361-93. 

A. Lykidis and S. Jackowski. 2000. Regulation of mammalian cell membrane biosynthesis Prog. Nucleic Acid Res. Mol. Biol. 65 361-393. (PubMed)... 

Enzymic lipid peroxidation reactions are a common reaction in mammalian cells as response to stress from outside. In contrast to plants mammalian cell membranes contain arachidonic acid instead of linolenic acid. The latter is known to generate by LPO processes physiological potent compounds prostaglandines, prostacyclines, thromboxanes and leukotiienes [221]. In addition a great number of other LPO products derived not only from arachidonic acid but also from linoleic acid have been detected in blood, especially low density lipoprotein (LDL) and tissue samples of humans [222-227]. These are increased especially in diseases combined with cell degradation [228], indicating that cell death in plant and mammalian cells is connected with a similar cascade of events. 

Phospholipids, glycolipids, and cholesterol are the major components of mammalian cell-membrane lipids. They... 

Polyenes are Streptomyces spp. derivatives whose primary mode of action is to bind preferentially to ergosterol in the fimgal cell membrane, disabling the organism by increasing membrane permeability and causing cell leakage. Polyenes also bind to cholesterol in mammalian cell membranes and this mechanism is probably responsible for their cytotoxicity. 

Boquet P, Pappenheimer AM Jr. (1976) Interaction of diphtheria toxin with mammalian cell membranes. J Biol Chem 215 5770-5778. 

In the previous two sections we discussed the electrodeformation and electroporation of vesicles made of single-component membranes in water. In this section, we consider the effect of salt present in the solutions. The membrane response discussed above was based on data accumulated for vesicles made of phosphatidylcholines (PCs), the most abundant fraction of lipids in mammahan cells. PC membranes are neutral and predominantly located in the outer leaflet of the plasma membrane. The inner leaflet, as well as the bilayer of bacterial membranes, is rich in charged lipids. This raises the question as to whether the presence of such charged lipids would influence the vesicle behavior in electric fields. Cholesterol is also present at a large fraction in mammalian cell membranes. It is extensively involved in the dynamics and stability of raft-hke domains in membranes [120]. In this section, apart from considering the response of vesicles in salt solutions, we describe aspects of the vesicle behavior of fluid-phase vesicles when two types of membrane inclusions are introduced, namely cholesterol and charged lipids. 

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