Sterol

About: Sterol is a research topic. Over the lifetime, 8117 publications have been published within this topic receiving 309926 citations. The topic is also known as: sterols & sterol lipids.

Functional interactions between sphingolipids and sterols in biological membranes regulating cell physiology

Abstract: Sterols and sphingolipids are limited to eukaryotic cells, and their interaction has been proposed to favor formation of lipid microdomains. Although there is abundant biophysical evidence demonstrating their interaction in simple systems, convincing evidence is lacking to show that they function together in cells. Using lipid analysis by mass spectrometry and a genetic approach on mutants in sterol metabolism, we show that cells adjust their membrane composition in response to mutant sterol structures preferentially by changing their sphingolipid composition. Systematic combination of mutations in sterol biosynthesis with mutants in sphingolipid hydroxylation and head group turnover give a large number of synthetic and suppression phenotypes. Our unbiased approach provides compelling evidence that sterols and sphingolipids function together in cells. We were not able to correlate any cellular phenotype we measured with plasma membrane fluidity as measured using fluorescence anisotropy. This questions whether the increase in liquid order phases that can be induced by sterol–sphingolipid interactions plays an important role in cells. Our data revealing that cells have a mechanism to sense the quality of their membrane sterol composition has led us to suggest that proteins might recognize sterol–sphingolipid complexes and to hypothesize the coevolution of sterols and sphingolipids.

Fibrates Suppress Bile Acid Synthesis via Peroxisome Proliferator–Activated Receptor-α–Mediated Downregulation of Cholesterol 7α-Hydroxylase and Sterol 27-Hydroxylase Expression

Abstract: Fibrates are hypolipidemic drugs that affect the expression of genes involved in lipid metabolism by activating peroxisome proliferator-activated receptors (PPARs). Fibrate treatment causes adverse changes in biliary lipid composition and decreases bile acid excretion, leading to an increased incidence of cholesterol gallstones. In this study, we investigated the effect of fibrates on bile acid synthesis. Ciprofibrate and the PPARα agonist Wy14,643 decreased bile acid synthesis in cultured rat hepatocytes and suppressed cholesterol 7α-hydroxylase and sterol 27-hydroxylase activities, paralleled by a similar reduction of the respective mRNAs. Treatment of rats with 0.05% (wt/wt) ciprofibrate decreased cholesterol 7α-hydroxylase enzyme activity and mRNA. The functional involvement of PPARα in the suppression of both enzymes was proven with the use of PPARα-null mice. In wild-type mice, ciprofibrate reduced cholesterol 7α-hydroxylase and sterol 27-hydroxylase enzyme activities and mRNA. The decrease in mRNA of both enzymes is regulated transcriptionally and posttranscriptionally, respectively, resulting in a decline in the output of fecal bile acids (-45%) and a 3-fold increase in fecal cholesterol secretion. These effects were completely abolished in PPARα-null mice. A decreased bile acid production by PPARα-mediated downregulation of cholesterol 7α-hydroxylase and sterol 27-hydroxylase may contribute to the increased risk of gallstone formation after fibrate treatment. Chemicals/CAS: Antilipemic Agents; Bile Acids and Salts; Cholesterol 7-alpha-Hydroxylase, EC 1.14.13.17; Cholesterol, 57-88-5; ciprofibrate, 52214-84-3; Clofibric Acid, 882-09-7; Cyp27a1 protein, mouse, EC 1.14.-; Cytochrome P-450 CYP27A1, EC 1.14.-; Cytochrome P-450 Enzyme System, 9035-51-2; pirinixic acid, 50892-23-4; Pyrimidines; Receptors, Cytoplasmic and Nuclear; RNA, Messenger; Steroid Hydroxylases, EC 1.14.-; Transcription Factors

beta-Sitosterol activates the sphingomyelin cycle and induces apoptosis in LNCaP human prostate cancer cells.

Abstract: Epidemiological evidence has shown that men consuming a low-fat, high-fiber diet containing high amounts of plant products have a lower risk of prostate cancer than men consuming a Western diet. One of the main differences between these two diets is the type of dietary fat, including dietary sterols. This study was undertaken to compare the effect of two dietary sterols on prostate cancer cells in vitro. beta-Sitosterol (SIT), the most common plant sterol, and cholesterol, an animal sterol, were compared for effect on LNCaP cell growth, differentiation, apoptosis, and sphingomyelin cycle intermediates. Cells were treated for up to seven days with sterols delivered by a cyclodextrin vehicle. Compared with cholesterol, SIT (16 microM) decreased growth by 24% and induced apoptosis fourfold, which was accompanied by cell rounding and a 50% increase in ceramide production. No effect was observed on differentiation as measured by prostate-specific antigen and prostatic acid phosphatase, although total acid phosphatase increased with SIT treatment for up to seven days. The results suggest that the decrease in cell number and increase in apoptosis associated with SIT treatment are mediated by activating the sphingomyelin cycle.

Cholesterol-lowering effects of plant sterol esters differ in milk, yoghurt, bread and cereal.

Abstract: Cholesterol-lowering effects of plant sterol esters differ in milk, yoghurt, bread and cereal