Cholesterol esters control

The stratum corneum consists of separated, nonviable, cornified, almost nonpermeable corneocytes embedded into a continuous lipid bilayer made of various classes of lipids, for example, ceramides, cholesterol, cholesterol esters, free fatty acids, and triglycerides [6], Structurally, this epidermis layer is best described by the so-called brick-and-mortar model [7], The stratum corneum is crucial for the barrier function of the skin, controlling percutaneous absorption of dermally applied substances and regulating fluid homeostasis. The thickness of the stratum corneum is usually 10-25 /an, with exceptions at the soles of the feet and the palms, and swells several-fold when hydrated. All components of the stratum corneum originate from the basal layer of the epidermis, the stratum germinativum. 

The intestinal absorption of dietary cholesterol esters occurs only after hydrolysis by sterol esterase steryl-ester acylhydrolase (cholesterol esterase, EC 3.1.1.13) in the presence of taurocholate [113][114], This enzyme is synthesized and secreted by the pancreas. The free cholesterol so produced then diffuses through the lumen to the plasma membrane of the intestinal epithelial cells, where it is re-esterified. The resulting cholesterol esters are then transported into the intestinal lymph [115]. The mechanism of cholesterol reesterification remained unclear until it was shown that cholesterol esterase EC 3.1.1.13 has both bile-salt-independent and bile-salt-dependent cholesterol ester synthetic activities, and that it may catalyze the net synthesis of cholesterol esters under physiological conditions [116-118], It seems that cholesterol esterase can switch between hydrolytic and synthetic activities, controlled by the bile salt and/or proton concentration in the enzyme s microenvironment. Cholesterol esterase is also found in other tissues, e.g., in the liver and testis [119][120], The enzyme is able to catalyze the hydrolysis of acylglycerols and phospholipids at the micellar interface, but also to act as a cholesterol transfer protein in phospholipid vesicles independently of esterase activity [121],... 

CRABP-GST is immobilized onto a glutathione-containing resin at a concentration that saturates the resin. A complex lipid mixture was prepared by combining a concentrated lipid extract derived from mouse tissue (brain) [5] (DMSO stock) with exogenously added retinoic acid (RA, positive control) and 13C-oleic acid (negative control). Analysis of this complex lipid mixture by LC-MS prior to incubation with immobilized CRABP demonstrated that the mixture contained RA (added), phospholipids, acylglycerols, cholesterol esters, and cholesterol. A portion of this mixture (corresponding to 1 nmol of RA) was added to PBS (DMSO concentration should not exceed 5%) and incubated with the CRABP-GST bound beads for 1 h. 

When the lipid content of the tonsils from E. L. was compared to a nonsymptomatic control, the main difference was a 50-fold increase in cholesterol esters. This finding prompted the investigators to focus their research on cholesterol metabolism in the probands. As all results of tests... 

Cholesterol ester content of the hepatocytes from oxysterol-fed rabbits was significantly higher then in control and purified cholesterol-fed rabbits [28] (Figure 11). 

Plasma levels of DHA, in cholesterol esters and phospholipids as well as erythrocyte phosphatidyl-choline and -ethanolamine, have been shown to be lower in patients with cystic fibrosis as compared with age-matched controls (Biggemann et al., 1988). Plasma phospholipid DHA has also been shown to be lower in well-nourished... 

Children with classical phenylketonuria (PKU) have reduced levels of DHA in plasma cholesterol esters (0.25 vs. 0.54 wt%) and membrane phospholipids compared with nonaffected controls (Sanjuro et al., 1994 Poge et al., 1998). It appears, however, that the reduced levels of DHA in PKU patients occur only in patients with strict diet therapy and are most probably caused by a reduced intake of omega-3 fatty acids (Poge et al., 1998). Studies are underway and planned on the effects of DHA supplementation in pregnant women with PKU and children with PKU (Giovannini et al., 1995). 

Fig. 3. Plasma cholesterol ester fatty acid increases in rats fed an eicosapentaenoic acid (EPAVy-linolenic acid (GLA) diet. Results are means SEM, n = 7, and are expressed as a percentage of control.

It appears there are two main reasons for the accumulation of cholesterol esters in rats that are fed HEAR oil or erucic acid containing diets. First, the cholesterol ester hydrolase fails to increase in activity when these rats are stressed, while in control rats, when stressed, the enzyme doubles its activity (Beckett and Boyd, 1975). Second, cholesteryl erucate, which accumulates in the adrenals of rats fed HEAR oil, is only slowly hydrolyzed by the enzyme, i.e., at 25-30% of the rate of cholesteryl oleate. This may be very significant, since there is considerable cholesteryl erucate accumulation in the adrenal glands of rats fed diets high in erucic acid, i.e., this ester may constitute 29-35% of the total (Carroll, 1962 Walker and Carney, 1971). In addition, in these rats there was an accumulation of 8% cholesteryl eicose-noate. In agreement with this evidence of impaired adrenal function, the results indicate that plasma levels of one of the adrenal hormones, corticosterone, are lower in these rats than in control rats when exposed to an environmental stress (Walker and Carney, 1971 Budzynska-Topolowska eta/., 1975). 

All defects can be picked up by a careful analysis of plasma cholesterol and its precursors by GC-MS. Following the saponification of cholesterol esters, the cholesterol(s) are extracted and derivatized to form trimethylsi-lyl ethers. The levels of all precursors are very low in controls, less than 1 pmol/l. Only few artefactual increases are known such as the increase of plant sterols (sitosterol) following the administration of intralipid, and the accumulation of 7- and 8-dehydrocholesterol following haloperidol drug treatment. 

The role of linoleate in cholesterol deposition and transport is not entirely clear. Kelsey and Longenecker (1941) proved that 62% of the plasma cholesterol of cattle occurred in combination with linoleate. It is only natural to postulate that, in the absence of EFA, cholesterol is deposited in the liver, because there is insufficient linoleate available to transport it to other tissues for metabolism and excretion. However, it has been shown that, in such conditions, the increased cholesterol is deposited in the liver as an ester. The cholesterol esters in the liver of rats have been proved to consist almost entirely of those of saturated and oleic acids only approximately 10% of the cholesterol occurs in combination with linoleic acid, irrespective of whether or not the diet contains EFA (Achaya et al., 1954a). It would thus appear that Unoleic acid is of prime importance in the control of the distribution and deposition of cholesterol in the rat. Whether or not the same situation obtains in the case of man is a moot question. 

Table 1). However, endotoxic VLDL was also prepared from rats treated with a lower dose of endotoxin (20 ig/kg body wt.) prior to liver perfusion myocardial accumulation of this low dose endotoxic VLDL was significantly less in perfused hearts (238 + 33 nmol/g wet wt. (n = 6)) than in control VLDL-perfused hearts (525 97 nmol/gwet wt. (n = 10) P < 0.05), This was due to deaeased accumulation of pH]TAQnd [sH] dia-cylglycerol but with no change in [ H]cholesterol ester, pH]NEFA and pH]phospholipid accumulation. Lipoprotein lipase activity was examined in heparin-releasable (endothe-... 

Palmitoleic acid and its ,3 homologue c/s-vaccenic acid (both n-1 monoene acids) have been reported to be inhibitors of mutagenesis and carcinogenesis (Hayatsu etal., 1988). Oral treatment with palmitoleic acid markedly prolonged the survival time of mice with Ehrlich ascites tumours, and the anti-tumour activity of palmitoleic acid is stronger than that of oleic acid (Ito et al., 1982). When palmitoleic acid-treated tumour cells were compared with control tumour cells, the total lipids and phospholipids contents were significantly lower and the fatty acid compositions of phosphatidylcholine, cholesterol esters, and triacylglycerols were considerably different (Ito et al., 1982). 

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