Cholesterol localization

In the field of lipids the only studies made until relatively quite recently were on frozen tissue sections, which ranged in thickness from 5 to 10 p. These were used in combination with emulsions in the form of stripping film which reduces the contrast of the preparation and makes more accurate localization quite difficult. Better resolution was sought by reducing the thickness of the section and application of liquid emulsion, and some improvement was obtained in the study of cholesterol localization in aorta (Charman and Lipsky, 1967). Another approach was the use of Carbowax, a water miscible wax, which allows the preparation of relatively thin sections (about 4 p). This method of tissue preparation was utilized for the study of phosphatidylinositol metabolism in the pancreas (Hokin and Hueb-ner, 1967) and of the distribution of cholesterol- in arteries and other tissues (Kramsch et al., 1967). The suitability of the Carbowax embedding for the study of lipids has been based on its being miscible with water and on the feasibility of performing lipid stains on sections prepared from Carbowax-embedded tissue. 

Bile acid synthesis from cholesterol is the prime pathway for cholesterol catabolism. Cholesterol is converted into bile acids via multiple pathways which involve 17 different enzymes. Many of these enzymes are predominantly expressed in the liver and are localized in several different subcellular... 

FIGURE 10.14 Schematic drawing showing the localization of xanthophyll molecules in the cholesterol-rich (raft or DRM) domain and the cholesterol-poor (bulk or DSM) domain. Unfavorable interaction with cholesterol in the cholesterol-rich domain is indicated. 

In addition to fluorescence methods, another study [27] developed a method to permit electron microscopic localization of Ras anchor domains on cytoplasmic membrane surfaces by immunogold labeling. The particle neighbor distances can be analyzed to obtain information about possible domain structure. Expressing H-Ras and K-Ras in baby hamster kidney cells, a nonrandom particle distribution was obtained from which the estimated mean raft size was 7.5-22 nm and about 35% of the membrane area consists of rafts. The same technique applied to cells that had been incubated with [3-cydodextrin to reduce cholesterol produced completely random distributions of H-Ras. This cholesterol dependence suggests some type of coupling of rafts across the inner and outer membrane leaflets. 

To explain the relationship between Lp(a) concentrations and risk of atherosclerosis, several hypothesis could be brought forward first, Lp(a) affects the metabolism of cholesterol and LDL secondly, Lp(a) plays a role in foam-cell and plaque formation thirdly, Lp(a) interacts with the activation of plasminogen to plasmin, the key step in the fibrinolytic system (L10, M27). Such activation can occur in two different localizations, i.e., on fibrin and its proteolytic residues, and on the surface of endothelial and monocytic cells. 

Cardiolipin or diphosphatidyl glycerol is one of the most ancient membrane phospholipids from phylogenic aspects. It is surprising for such a complex molecule as cardiolipin to have evolved as one of the major membrane lipids in prokaryotics, when steroids such as cholesterol and phytosterols did not. In eukaryotic cells, cardiolipin is exclusively localized within the mitochondria where it is particularly emiched in the outer leaflet of the inner membrane. Even though a molecular structure of cardiolipin has been conserved in entire organisms, its biological significance has escaped attention except in the case of anti-cardiolipin auto-antibodies which are clinically associated with the Wasserman reaction. 

In common with the polylysine DNA-condensing peptide, the p peptide has also been shown to have nuclear localization properties. Confocal microscopy revealed that p peptide in a complex containing fluorescent lipid- and dye-labelled DNA associates with the nuclei and nucleoli of both dividing and nondividing cells within 15 minutes of exposure to the complex, thus suggesting an NLS function. However, this property was not detectable when the peptide became incorporated into a 3p-[N-(N, N -dimethylaminoethane)-carbamoyl]-cholesterol (DC-chol)/DOPE cationic liposome (149). It may be the case that the lipids may mask the critical residues. 

Runz, H., Rietdorf, J., Tomic, I., et al. (2002) Inhibition of intracellular cholesterol transport alters presenihn localization and amyloid precursor protein processing in neuronal cells. J. 

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