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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mammalian cells require cholesterol as a structural component of plasma membranes. It is also required for placental steroid synthesis. De novo synthesis of cholesterol is limited in human placenta and cholesterol is obtained mainly from plasma low density lipoprotein (LDL). Cholesterol delivery from LDL is mediated by receptor-mediated uptake and the receptor amount is the most important factor for cellular delivery. Thus, the regulation of receptor synthesis is important for placental development and function. Since the regulation of LDL receptor gene expression has not been studied in human placenta, LDL receptor mRNA was measured in placentae of 5-40 weeks of gestation by hybridization of RNA with 32P-labeled cDNA for human LDL receptor. Two mRNA species for LDL receptor were demonstrated by Northern blot analysis. The longer mRNA [5.3 kilobases (kb)] was much more abundant than the shorter mRNA (3.7 kb). The amount of 5.3 kb mRNA was highest early in gestation and decreased during pregnancy. However, the amount of 3.7 kb mRNA did not change appreciably during gestation. Dot blot analysis of 26 placental mRNAs obtained from various stages of gestation revealed a negative correlation between LDL receptor mRNA and gestation (r = -0.76, P less than 0.001). Considering the rapid growth of the trophoblast during gestation, especially in the first and the second trimester, increased expression of the LDL receptor gene and subsequent translation are expected for efficient cholesterol uptake to provide a sufficient substrate for cell growth. Possible mechanisms for the appearance of two mRNA species for LDL receptor are also discussed.
Mol Endocrinol 1989 Aug
PMID:Expression of low density lipoprotein receptor gene in human placenta during pregnancy. 257 Oct 80

Compositional and maturative parameters of high density lipoproteins (HDL) have been examined during the early stages of rat liver regeneration, when lecithin:cholesterol acyltransferase (LCAT) activity, responsible for the maturation of this lipoprotein class, is markedly decreased. Both HDL subclass distribution and chemical composition are not significantly different from the control, except for a slightly lower cholesterol ester content. Few disc-shaped particles are detectable by electron microscopic observation. Cholesterol ester decrease and presence of immature particles are related, but the entity of the modification is lower than suggested by the deep decrease of LCAT activity. This seems to indicate that proper HDL maturation is assured in the regenerating liver despite low LCAT activity.
Cell Mol Biol 1989
PMID:High density lipoproteins during rat liver regeneration. 270 53

Rat adrenal mitochondria exhibit a linear 2-fold accumulation of cholesterol for 20 min following either in vivo ether stress or ACTH administration, providing cholesterol metabolism is inhibited by aminoglutethimide (AMG). Additional cycloheximide (CX) pretreatment only slightly decreases this increase, but the location of accumulation shifts from the inner membrane to the outer membrane, implying a decreased cholesterol transfer from outer to inner membrane. Although the capacity of outer mitochondrial membranes was saturated after a 10-min treatment with CX, a 20-min treatment resulted in further retention of cholesterol in intact mitochondria that was not recovered in the isolated membranes. An additional pool of loosely bound cholesterol is proposed for CX mitochondria. These studies provide evidence that the CX-sensitive step of adrenal steroidogenesis attributed to loss of a labile ACTH regulatory protein (Pedersen, R.C. and Brownie, A.C. (1983) Proc. Natl. Acad. Sci. U.S.A. 80, 1882-1886) involves cholesterol transfer from the outer to the inner mitochondrial membrane. ACTH also enhances the PI and PE content of the outer membranes by a CX-sensitive mechanism that may contribute to intramitochondrial cholesterol transport. CX treatment does not affect cholesterol uptake by the inner membrane from phospholipid vesicles. The initial rate of endogenous metabolism in isolated inner membranes is insensitive to pretreatment (2 nmol/nmol P-450/min). The duration of this linear rate was increased 4-fold by AMG treatment while this increase was prevented by CX treatment. The kinetics indicate differences in inner membrane reactive cholesterol levels. Inner membranes also contained a fraction of unreactive cholesterol that is insensitive to pretreatment. Cholesterol-P-450scc complex formation for all pretreatments fits a single hyperbolic function of the reactive cholesterol content of the inner mitochondrial membrane (Kd = 0.025 mol cholesterol/mol phospholipid), and is activated over 5-fold upon mitochondrial disruption. All changes in inner membranes caused by CX can, therefore, be attributed solely to the restricted cholesterol access in vivo.
Mol Cell Endocrinol 1987 Sep
PMID:ACTH control of cholesterol side-chain cleavage at adrenal mitochondrial cytochrome P-450scc. Regulation of intramitochondrial cholesterol transfer. 282 9

The present study provides a histochemical analysis of the macromolecular and cellular composition of focal and segmental glomerular hyalinosis and sclerosis (FSGHS) in the rat with special reference to the different types of lipids present and to the participation of monocytes. FSGHS was induced in male Wistar rats by unilateral nephrectomy (UN) or puromycin aminonucleoside (PAN) injections. Histochemical analysis of glomeruli with FSGHS in both models after 20 weeks of proteinuria revealed massive deposits of lipids. These lipid accumulations were shown to consist mainly of free and esterified cholesterol; triglycerides and phospholipids were present in small amounts. Monocytes, identified by the alpha-naphthyl acetate method for non-specific esterase activity were scanty in glomeruli affected by FSGHS with an average glomerular count of 0.1 in UN- and 0.2 in PAN-treated rats. When present, no preferential localization of monocytes in the lesions was observed. The progressive glomerular damage occurring once the process of hyalinosis and sclerosis has started may be related to the paucity of "scavenging" monocytes. Cholesterol may be one of the substances involved in the development of these glomerular changes.
Virchows Arch B Cell Pathol Incl Mol Pathol 1986
PMID:Glomerular sclerotic lesions in the rat. Histochemical analysis of their macromolecular and cellular composition. 287 25

The effect of hypertension, hyperlipidemia, and the combination of both on acute and chronic myocardial ischemia were evaluated in a total of 30 male rabbits. After preliminary hypertension and/or hyperlipidemic load by loading of the abdominal aorta and/or cholesterol feeding, acute ischemia was produced by clipping of the left coronary artery. The banding produced elevation of carotid arterial pressure and left ventricular hypertrophy. Cholesterol feeding resulted in severe atheromatous changes in all sizes of coronary arteries. The intimal thickening was due to foam cell accumulation in all arteries examined. Animals pretreated with the combination of hypertension and hyperlipidemia displayed the most severe cardiolmegaly with advanced coronary atherosclerosis and chronic ischemic lesions of the myocardium, i.e., perivascular patchy fibrosis in the subendocardial area. Furthermore, electron microscopic detection of ultrastructural myocardial damage, involving glycogen depletion, sarcoplasmic edema, mitochondrial swelling, and contractile abnormalities, was also most frequent in this group. These changes were quantitated using the ischemic score. These results confirm the hypothesis that fatal ischemic injuries may occur clinically in human hearts with coronary insufficiency due to coexistence of hypertensive cardiomegaly and severe coronary atherosclerosis. They offer a model for further study of these combined effects.
Exp Mol Pathol 1985 Apr
PMID:An ultrastructural study on ischemic lesions in rabbits' hearts with pressure overload and hyperlipidemia. 315 60

Cholesterol-ladened plasma membrane vesicles were used to load smooth muscle cells (SMC) with cholesterol. Plasma membrane vesicles (PMV) were isolated from rabbit atherosclerotic lesions, and characterized as to size, cholesterol content, and marker enzyme (plasma membrane, lysosome, endoplasmic reticulum) composition. PMV were regarded as a necrotic product since they are produced upon injury to cells. Degradation of PMV was proportional to the PMV protein concentration in the culture medium, suggesting bulk intake of PMV. Cholesterol accumulation of SMC varied with the cholesterol content of the vesicle. Incubation for 3 days with PMV having 0.39 and 0.62 mg cholesterol/mg protein induced the accumulation of 8 and 29 micrograms of esterified cholesterol/mg cell protein, respectively. Incorporation of oleate into cholesteryl ester during a 24-hr period under these conditions, however, was the same. The contribution of cholesterol ester synthesis to the esterified cholesterol content of SMC was 40 and 11% of the total when exposed to PMV having, respectively, low and high contents of cholesterol. This study suggests that cholesterol-bearing PMV in lesions can be utilized to load lesion-SMC. These observations suggest that lipid-bearing elements other than low density lipoprotein may be responsible for cholesterol-loaded SMC in lesions.
Exp Mol Pathol 1988 Oct
PMID:Cholesteryl ester accumulation in smooth muscle cells after uptake of necrotic products from atherosclerotic lesions. 316 5

The effects of LDL and Ac-LDL on the growth properties, morphology, and cholesteryl ester (CE) metabolism of the RAW264 macrophage cell line have been characterized. Cells were grown in media supplemented by a defined media (DM) mixture or fetal bovine serum (FBS). The addition of LDL or Ac-LDL to the culture media did not significantly alter cell growth properties. Cytoplasmic deposition of CE was observed by fluorescence microscopy in macrophages treated with LDL or Ac-LDL but not in untreated controls. Dose-response studies have shown that cholesteryl ester (CE) can accumulate in RAW264 treated with LDL. Cellular cholesterol content saturated at 4 hours with 50 micrograms/ml LDL; this effect may be associated with receptor saturation. Dose-response studies conducted with Ac-LDL in DM have shown dramatic increases in total cell cholesterol content. However, deposition of CE was not observed below Ac-LDL concentrations of 100 micrograms/ml. This indicates that a critical concentration of Ac-LDL must be reached to trigger deposition in DM. In contrast, no critical concentration of Ac-LDL was observed in macrophages grown in medium supplemented with 10% FBS. Cholesterol esterification in response to LDL and Ac-LDL was examined by 14C-oleic acid incorporation into CE. These results confirmed the mass cellular cholesterol and CE measurements. Kinetic studies conducted with RAW264 cells treated with 50 or 100 micrograms/ml Ac-LDL resulted in a cholesterol efflux from the cells at 6-12 hours of incubation. Therefore, these studies show that (1) the nature of CE deposition is highly dependent upon the incubation media and (2) CE deposition is very sensitive to Ac-LDL concentration under certain conditions.
Mol Cell Biochem 1988 Nov
PMID:Cholesteryl ester handling by RAW264 macrophages: response to native and acetylated low density lipoprotein. 323 Dec 15

Cholesterol crystals activate the human alternative complement pathway. Loss of Factor B hemolytic activity in C2-deficient serum was comparable to that in normal human serum after incubation with cholesterol crystals. Consumption of Factor B hemolytic activity in normal serum incubated with cholesterol occurred in a time- and dose-dependent manner. The reduced capacity of crystals-absorbed serum to activate C2, but not Factor B, on fresh crystals, indicated that cholesterol mediates antibody-dependent classical pathway activation in addition to alternative pathway activation in whole serum. Cholestane triol, an oxidation derivative of cholesterol which bears three hydroxyl groups, cleaved 5-fold more C3 than cholesterol in normal human serum. Three cholesterol derivatives, each bearing two hydroxyl groups, were intermediate activators between cholesterol and cholestane triol. The compounds differed, however, in their complement-activating ability, indicating that hydroxyl position as well as number exerts an influence on complement activation. Measurements of C3adesArg and C5adesArg antigens in cholesterol crystal treated serum revealed that approx. 10% of total serum C3 was cleaved and that, on a molar basis, only 3% C5 cleavage occurred relative to C3 cleavage. For 1 mole of C5a generated, 0.1 moles of fluid-phase C5b-9 was detected. Although the extent of C3 cleavage varied with each cholesterol derivative depending on the position and number of hydroxyl groups, the relative coupling efficiency of C3 and C5 cleavage and C5a and C5b-9 generation was similar for all compounds. The ability of cholesterol and its oxidation products to generate anaphylatoxins and C5b-9 complexes may be of importance in mediating inflammatory processes involved in atherogenesis.
Mol Immunol 1987 Dec
PMID:Generation of complement anaphylatoxins and C5b-9 by crystalline cholesterol oxidation derivatives depends on hydroxyl group number and position. 343 52

Lipids extracted from whole worm homogenates and tegumental outer membranes of guinea pig-derived 5-day, 2-, 3- and 6-week old schistosomes have been analysed by thin layer chromatography. Six-week hamster-derived parasites have been studied for comparative purposes. All homogenates contained neutral lipids, cholesterol and several phospholipids; phosphatidyl choline and phosphatidyl ethanolamine were major components. Phospholipid (P3) was absent from homogenates of 5-day worms but was present in older parasites. A single phospholipid (P4) which co-chromatographed with phosphatidyl glycerol was unique to hamster-derived parasites. One glycolipid (G1) was ubiquitous to all homogenates and co-chromatographed with the monogalactosyl ceramide marker. A second sugar-containing lipid (G2) was unique to 3-week worm homogenates, and was highly polar. It was resolved beneath the trigalactosyl ceramide marker. Tegumental membranes isolated from 6-week adults contained at least five glycolipids, four of which were also highly polar. Cholesterol and two dominant phospholipids occurred in the membranes of 2-, 3-, and 6-week worms. One phospholipid co-chromatographed with phosphatidyl choline; the other had an Rf value (relative band speed) equivalent to phosphatidyl ethanolamine. Membranes from liver stage parasites contained a further phospholipid which cochromatographed with sphingomyelin, and three additional, phosphate-staining lipids (P1, P3 and P6). Five sugar-containing lipids occurred in adult membranes only; four were highly polar, being resolved near the origin. Similar components were identified in extracts of host erythrocytes. The remaining membrane lipid appeared homologous to G1 identified in the whole worm homogenates. Important changes in lipid composition thus occur during schistosome growth and maturation in guinea pigs; moreover, worms derived from different rodents express different lipids.
Mol Biochem Parasitol 1987 Jan 15
PMID:Analysis of total and surface membrane lipids of Schistosoma mansoni. 357 47

The luminal surface properties of aortic and mitral valve endothelium in hypercholesterolemic rabbits were examined with the aid of cationic ferritin (CF), ferritin-lectins (FWGA, FRCA, FSBA), and low density lipoprotein-colloidal gold (LDL-Gold) conjugates. Based upon comparative studies with normocholesterolemic rabbit valves, the number of CF and wheat germ agglutinin (FWGA) particles per 100 nm of endothelial surface was found to be reduced in moderate hypercholesterolemia (450 mg/dl). Conversely, the number of Ricinus communis agglutinin (FRCA) and soybean agglutinin (FSBA) conjugates were increased. Quantitation of the CF and FWGA particles demonstrated that the endothelium lining of the valve surfaces (i.e., the arterial surfaces of the aortic cusps, AA, and the ventricular surfaces of the mitral cusps, MV) exposed to more turbulent hemodynamic conditions displayed the greatest densities of particle counts. Cholesterol levels of 400-500 mg/dl produced a loss of characteristic differences in the number of ferritin particles that existed between the two surfaces of a cusp. Especially prominent over the AA and MV surfaces, these changes represented a reduction in the anionic properties of the endothelial glycocalyx. Enzymatic digestion demonstrated the reduction in surface sialic acid residues to be one of the major factors responsible for these early changes at the blood-endothelium interface. More severe hypercholesterolemia (700-900 mg/dl) resulted in even further reductions in the number of ferritin particles over the AA and MV surfaces but enhanced the binding of LDL-Gold. Chondroitinase studies of these specimens demonstrated that the initial loss of sialic acids at moderate serum levels unmasks deeper lying components of the glycocalyx (e.g., sulfated glycosaminoglycans) and augments the attachment of LDL molecules to the endothelial surface. The findings of this study suggest that specific macromolecular changes in the endothelial glycocalyx in diet-induced hypercholesterolemia occur at vascular locales where hemodynamic forces such as eddy formations and blood stagnation impinge against the vascular wall.
Exp Mol Pathol 1986 Jun
PMID:A cytochemical study of the surface properties of aortic and mitral valve endothelium from hypercholesterolemic rabbits. 372 Sep 17


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