Marked elevation of HDL-cholesterol in cold-adapted golden hamsters

Golden hamsters with spontaneous hypercholesterolemia at 22 degrees C developed a further increase in plasma cholesterol when they were maintained at 6 degrees C. This hypercholesterolemia was associated with a redistribution of plasma cholesterol between VLDL and HDL. Plasma cholesterol transported in the VLDL decreased while cholesterol in the HDL increased by 45%. The LDL profile was not significantly modified.     

The rate of biliary cholesterol secretion in high- and low-responding rhesus monkeys

The rates of secretion of cholesterol in bile measured by an isotope ratio method were found similar in cholesterol-fed high- and low-responding rhesus monkeys. The results indicate that the failure on the part of the high-responders to increase proportionately the fecal excretion of neutral steroids to compensate for the higher absorption of cholesterol than the low-responders, as suggested earlier, is not due to a difference in the rate of biliary cholesterol secretion but must lie in some other aspect of cholesterol metabolism.     

Marked elevation of HDL-cholesterol in cold-adapted golden hamsters

Summary Golden hamsters with spontaneous hypercholesterolemia at 22°C developed a further increase in plasma cholesterol when they were maintained at 6°C. This hypercholesterolemia was associated with a redistribution of plasma cholesterol between VLDL and HDL. Plasma cholesterol transported in the VLDL decreased while cholesterol in the HDL increased by 45%. The LDL profile was not significantly modified.     

Demonstration of a cytosol protein binding cholesterol in the adrenal glands]

Characterization of a cytosolic protein of adrenal origin that binds cholesterol. Adrenal cytosol contains a thermostable protein which binds cholesterol specifically and non-covalently. The sedimentation coefficient of the complex is close to 3 S. The side chain of the cholesterol molecule is responsible for the binding specificity.     

Cholesterol content and cholesterol esterifying activity of various organs in guinea pigs

In various organs of the guinea pig, the total cholesterol content of an organ was significantly correlated with the percentage of esterified cholesterol present in this organ. Cholesterol esterifying capacity was shown in most organs, with highest activities in the adrenals, the spleen and the liver. The significant correlation found between the cholesteryl ester content of an organ and its acyl cholesterol acyltransferase activity suggests a possible role of this enzyme in determining the level of the total and esterified cholesterol in a tissue.     

Cholesterol feeding to rats does not modulate the expression of binding sites for HDL on liver membranes

The binding of HDL, Apo-E-free, was studied in rats fed a cholesterol rich diet for 2, 4 and 7 days. Plasma cholesterol increased up to 16-fold (from 55 to 900 mg/dl); liver cholesterol was also raised, from 0.5 to 16 mg/g of tissue. The HDL binding to membrane preparations was not affected while the binding of beta VLDL was reduced to about 50% of the controls. These data show, therefore, that liver binding sites for HDL are refractory to regulation by dietary cholesterol.     

Effects of plant sterols on cholesterol concentration in the rat small intestine

Summary The effects of feeding single doses of -sitosterol, campesterol and stigmasterol on cholesterol concentration in the rat small intestine was studied to clarify their roles in cholesterol absorption. The different plant sterols affected free and ester cholesterol concentrations differently in the different intestinal segments suggesting that they have different effects on such intestinal processes as uptake, esterification and possibly synthesis of cholesterol and transport of cholesterol esters out of the mucosal cells into the lymphatics.Acknowledgments. Financed by the Emergy Goff Research Award from the American Heart Association-Louisiana, Inc. and the NHLBI research grant HL-08974 from the National Institutes of Health, Bethesda, Maryland.     

Effect of preoperative stress on serum cholesterol level in humans

Summary Effect of preoperative stress on serum cholesterol level in 65 patients of different age groups in a surgical ward, has been studied. In all age groups, statistically significant rise of cholesterol in serum preoperatively was noticed as compared with serum cholesterol level at the time of discharge from hospital. The preoperative rise of cholesterol varied from 39 to 56.9% in this series. These findings support previous reports of the effect of mental tension on serum cholesterol level.Authors acknowledge with pleasure the useful discussions with Dr A. K. Ganguly, Prof. of Physiology, Government Medical College, Surat, Dr T. H. Rindani, Medical Director, Jaslok Hospital, Bombay. Statistical analysis by Shri P. Gopinath and technical assistance of Shri N. T. Pabani.     

The role of cholesterol in Shh signaling and teratogen-induced holoprosencephaly

Holoprosencephaly, or an undivided forebrain, is a complex brain malformation associated with Sonic hedgehog (Shh) mutations. Other causes of holoprosencephaly have converged upon the Shh signaling pathway: genetic and pharmacologic impairment of cholesterol synthesis, and the action of the steroidal alkaloid cyclopamine. This review focuses on recent studies aimed at determining how Shh signaling is affected by these causes of holoprosencephaly, whether they involve a common mechanism and the role played by cholesterol. Cholesterol is potentially important for both biogenesis of Shh and in signal transduction in Shh-responsive cells. Teratogens that induce holoprosencephaly appear to affect Shh signal transduction rather than Shh biogenesis. Analysis of these agents and other compounds that affect various aspects of cellular cholesterol distribution indicates that the role of cholesterol in Shh signal transduction is novel and complicated. The similarity of the Shh receptor, Patched (Ptc), to the Niemann-Pick Cl protein, which is involved in the vesicular trafficking of cholesterol, provides insight into the role of cholesterol and the action of compounds like cyclopamine.     

Mylip makes an Idol turn into regulation of LDL receptor

High blood low-density-lipoprotein (LDL) cholesterol is a serious health problem among an increased number of patients in the Western world. Statins and other cholesterol lowering drugs have proven to be beneficial as therapy but are not optimal and show adverse effects in some patients. The LDL receptor is a crucial determinant of cholesterol metabolism in the body and amenable for drug interventions. Novel insights into the physiology of this receptor come from studies on the ubiquitination and degradation of LDL receptor by the ubiquitin ligase Mylip/Idol that is induced in cells by the nuclear receptor, LXR. This may open up new possibilities in the future to influence LDL receptor levels and cholesterol metabolism pharmacologically in various diseases.     

Cholesterol feeding to rats does not modulate the expression of binding sites for HDL on liver membranes

Summary The binding of HDL, Apo-E-free, was studied in rats fed a cholesterol rich diet for 2, 4 and 7 days. Plasma cholesterol increased up to 16-fold (from 55 to 900 mg/dl); liver cholesterol was also raised, from 0.5 to 16 mg/g of tissue. The HDL binding to membrane preparations was not affected while the binding of VLDL was reduced to about 50% of the controls. These data show, therefore, that liver binding sites for HDL are refractory to regulation by dietary cholesterol.     

Regulation of receptor function by cholesterol

Cholesterol influences many of the biophysical properties of membranes and is nonrandomly distributed between cellular organelles, subdomains of membranes, and leaflets of the membrane bilayer. In combination with the high dynamics of cholesterol distribution, this offers many possibilities for regulation of membrane-embedded receptors. Depending on the receptor, cholesterol can have a strong influence on the affinity state, on the binding capacity, and on signal transduction. Most important, cholesterol may stabilize receptors in defined conformations related to their biological functions. This may occur by direct molecular interaction between cholesterol and receptors. In this review, we discuss the functional dependence of the nicotinic acetylcholine receptor as well as different G protein-coupled receptors on the presence of cholesterol.     

MDR1, cholesterol certification and cell growth: a comparative study in normal and multidrug-resistant KB cell lines

The product of the MDR1 gene (P-gp) has been implicated in the transport of cholesterol from plasma membrane to endoplasmic reticulum for esterification. In previous studies on leukemia cell lines, we suggested that cholesterol esterification may regulate the rate of cell growth and that the MDR1 gene might be involved in this process by modulating intracellular cholesterol esters levels. To further investigate this matter, the rate of cell growth, cholesterol metabolism, expression of the MDR1 gene, and P-gp activity were compared in KB cell lines displaying differences in expression and function of P-gp (drug-sensitive phenotype versus MDR phenotype). The rate of cell growth correlated with cholesterol esterification in all KB cell lines, whereas the over-expression of MDR1 observed in the MDR cell lines was not always associated with an increased capacity of cells to esterify cholesterol. Two known inhibitors of P-gp activity, progesterone and verapamil, strongly inhibited both cholesterol esterification and cell proliferation in all KB cell lines, but they affected intracellular accumulation of labeled vinblastine only in MDR cell lines. These results further support a role for cholesterol esters in the regulation of cell growth and suggest that the P-gp expressed in MDR KB cells is not involved in the general process leading to cholesterol esterification. Received 14 February 2000; received after revision 10 April 2000; accepted 8 May 2000     

K-p-nitrophenylphosphatase activity, Na and K content, Na permeability and membrane lipid composition in rabbit myocardium after cholesterol rich diet

The aim of the present study was to investigate the effects of a cholesterol-rich diet on membrane function and lipid composition in rabbit myocardium. The activity and the ouabain sensitivity of the K-p-nitrophenylphosphatase (K-pNPPase), a partial reaction of the Na, K-ATPase, were diminished after a cholesterol/oil or pure cholesterol diet. The content of cholesterol, cholesterol esters and of several classes of phospholipids was enhanced in microsomes. A causal relationship is assumed between cholesterol accumulation and a decrease in membrane fluidity as well as in Na, K-ATPase activity. The intracellular Na content and the Na-Li-exchange rate were higher after the cholesterol diet. The increase in the Na content is supposed to be induced by a lower Na transport and a higher Na permeability. An enhanced Ca flux via the sarcolemma could be the consequence.     

Concentration of ‘available’ unesterified cholesterol in human plasma as evaluated from inhibition of hemolysis by lucensomycin

Summary The unesterified cholesterol content of plasma samples can be evaluated from the extent of inhibition of lucensomycin-induced hemolysis. The test measures, however, only the fraction of cholesterol which is available for interaction with lucensomycin, this availability being adversely affected by high phospholipid-cholesterol ratios.     

K-p-Nitrophenylphosphatase activity,Na and K content,Na permeability and membrane lipid composition in rabbit myocardium after cholesterol rich diet

Summary The aim of the present study was to investigate the effects of a cholesterol-rich diet on membrane function and lipid composition in rabbit myocardium. The activity and the ouabain sensitivity of the K-p-nitrophenylphosphatase (K-pNPPase), a partial reaction of the Na, K-ATPase, were diminished after a cholesterol/oil or pure cholesterol diet. The content of cholesterol, cholesterol esters and of several classes of phospholipids was enhanced in microsomes. A causal relationship is assumed between cholesterol accumulation and a decrease in membrane fluidity as well as in Na, K-ATPase activity. The intracellular Na content and the Na-Li-exchange rate were higher after the cholesterol diet. The increase in the Na content is supposed to be induced by a lower Na transport and a higher Na permeability. An enhanced Ca flux via the sarcolemma could be the consequence.To whom reprints should be addressed     

Hypolipidemic effects of garlic oil in rats fed ethanol and a high lipid diet

Summary Feeding of ethanol and a high fat-high cholesterol diet to rats markedly increased the total lipids in the liver, and cholesterol and triglyceride levels in the serum, liver and kidneys. However, when ethanol mixed with 0.5% garlic oil was fed to animals maintained on the high fat-high cholesterol diet, these lipid levels were significantly reduced to levels near to those seen in untreated control rats. Garlic oil did not reduce the serum albumin or the total proteins of liver, kidneys or serum when fed along with ethanol. Probably the garlic oil enhances the catabolism of dietary cholesterol and fatty acids.The authors acknowledge with thanks the financial assistance of the University of Maiduguri for carrying out this project.     

Challenges and approaches to understand cholesterol-binding impact on membrane protein function: an NMR view

Experimental evidence for a direct role of lipids in determining the structure, dynamics, and function of membrane proteins leads to the term ‘functional lipids’. In particular, the sterol molecule cholesterol modulates the activity of many membrane proteins. The precise nature of cholesterol-binding sites and the consequences of modulation of local membrane micro-viscosity by cholesterol, however, is often unknown. Here, we review the current knowledge of the interaction of cholesterol with transmembrane proteins, with a special focus on structural aspects of the interaction derived from nuclear magnetic resonance approaches. We highlight examples of the importance of cholesterol modulation of membrane protein function, discuss the specificity of cholesterol binding, and review the proposed binding motifs from a molecular perspective. We conclude with a short perspective on what could be future trends in research efforts targeted towards a better understanding of cholesterol/membrane protein interactions.