Effects of brefeldin A and nordihydroguaiaretic acid on endomembrane dynamics and lipid synthesis in plant cells.
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Effects of brefeldin A (BFA) and nordihydroguaiaretic acid (NDGA) on endomembrane structures and lipid synthesis were compared in maize root cells and tobacco Bright Yellow-2 cells. Immunofluorescence and electron microscopy studies showed that NDGA altered the structure and distribution of the endoplasmic reticulum (ER) within 1 h but not of the Golgi apparatus whereas, as shown previously, BFA altered that organization of the Golgi apparatus and, only subsequently, of the ER. Biochemical studies revealed that both drugs and especially BFA led to a strong inhibition of the phytosterol biosynthetic pathway: BFA led to accumulation of sterol precursors. The importance of phytosterols in membrane architecture and membrane trafficking is discussed. (+info)
BES1 accumulates in the nucleus in response to brassinosteroids to regulate gene expression and promote stem elongation.
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Plant steroid hormones, known as brassinosteroids (BRs), signal through a plasma membrane localized receptor kinase BRI1. We identified bes1, a semidominant suppressor of bri1, which exhibits constitutive BR response phenotypes including long and bending petioles, curly leaves, accelerated senescence, and constitutive expression of BR-response genes. BES1 accumulates in the nucleus in response to BRs. BES1 is phosphorylated and appears to be destabilized by the glycogen synthase kinase-3 (GSK-3) BIN2, a negative regulator of the BR pathway. These results establish a signaling cascade for BRs with similarities to the Wnt pathway, in which signaling through cell surface receptors leads to inactivation of a GSK-3 allowing accumulation of a nuclear protein that regulates target gene expression. (+info)
Micellar distribution of cholesterol and phytosterols after duodenal plant stanol ester infusion.
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Properties of the intestinal digestion of the dietary phytosterols, cholesterol and cholestanol, and the mechanisms by which phytosterols inhibit the intestinal absorption of cholesterol in healthy human subjects are poorly known. We have studied the hydrolysis of dietary plant sterol and stanol esters and their subsequent micellar solubilization by determining their concentrations in micellar and oil phases of the jejunal contents. Two liquid formulas with low (formula 1) and high (formula 2) plant stanol concentrations were infused via a nasogastric tube to the descending duodenum of 8 healthy human subjects, and intestinal contents were sampled for gas-liquid chromatographic sterol analysis 60 cm more distally. During the duodenal transit, phytosterol esters were hydrolyzed. This was especially profound for sitostanol, as its esterified fraction per milligram of sitosterol decreased 80% (P < 0.001) in formula 1 and 61% (P < 0.001) in formula 2. Contrary to that, esterified fraction of cholesterol per milligram of sitosterol was increased fourfold (P < 0.001) in formula 1 and almost sixfold (P < 0.001) in formula 2, whereas that of cholestanol remained unchanged. Percentages of esterified sterols and stanols in total intestinal fluid samples were higher after the administration of formula 2 than of formula 1. Esterified cholesterol and stanols accumulated in the oil phase, and free stanols replaced cholesterol in the micellar phase. At high intestinal plant stanol concentrations, cholesterol looses its micellar solubility possibly by replacement of its free fraction in the micellar phase by hydrolyzed plant stanols, which leads to a decreased intestinal absorption of cholesterol. (+info)
Phytosterols that are naturally present in commercial corn oil significantly reduce cholesterol absorption in humans.
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BACKGROUND: Although supplementing the diet with large quantities of phytosterols reduces cholesterol absorption and LDL-cholesterol concentrations, very little is known about the smaller amounts of phytosterols present naturally in food. Vegetable oils are the richest dietary source of phytosterols; corn oil contains 0.77% phytosterols by weight. OBJECTIVE: We tested the hypothesis that removing phytosterols from corn oil would increase cholesterol absorption when measured in single-meal tests containing corn oil as a source of fat. DESIGN: Free and esterified phytosterols were removed from corn oil on a kilogram scale by a new technique of competitive saturation adsorption to silica. Healthy subjects with a mean (+/-SEM) serum cholesterol concentration of 5.10 +/- 0.18 mmol/L received an otherwise sterol-free test breakfast on 2 occasions 2 wk apart that contained 35 mg hexadeuterated cholesterol and 30-35 g of a corn oil preparation. The plasma enrichment of tracer was measured by negative ion mass spectrometry. RESULTS: Cholesterol absorption was 38.0 +/- 10.2% higher after consumption of the sterol-free corn oil than after consumption of commercial corn oil with an identical fatty acid content (P = 0.005; n = 10). When corn oil phytosterols were added back to sterol-free corn oil at a concentration of 150 mg/test meal, cholesterol absorption was reduced by 12.1 +/- 3.7% (P = 0.03; n = 5) and by 27.9 +/- 9.1% (P = 0.01; n = 10) after inclusion of 300 mg phytosterols. CONCLUSIONS: Phytosterols comprising < 1% of commercial corn oil substantially reduced cholesterol absorption and may account for part of the cholesterol-lowering activity of corn oil previously attributed solely to unsaturated fatty acids. (+info)
Influence of phytostanol phosphoryl ascorbate, FM-VP4, on pancreatic lipase activity and cholesterol accumulation within Caco-2 cells.
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PURPOSE: The objective of this study was to determine how a novel hydrophilic phytostanol (FM-VP4) affects the cellular accumulation of [3H]cholesterol in human colon carcinoma (Caco-2) cell monolayers grown in Transwell chambers. METHODS: To determine cellular accumulation of cholesterol and FM-VP4, [3H]cholesterol- containing micelles (50 microM cholesterol containing 1.27x10 (-4)% [3H]cholesterol) or [3H]FM-VP4 (50 microM) was incubated on the apical side of differentiated Caco-2 cell monolayers for 1 to 4 h at 37 degrees C in the absence or presence of increasing concentrations (10-200 microM) of unlabeled FM-VP4 or cholesterol, respectively. RESULTS: The accumulation of [3H]cholesterol (presented in micelles) into Caco-2 cell monolayers in the presence of 50 microM FM-VP4 was significantly lower (33.7 +/- 7.0%) compared to control (59.8 +/- 5.2%, p<0.05) following 4 h of incubation. Conversely, cholesterol inhibited the accumulation of [3H]FM-VP4, although to a lesser extent, suggesting competition for binding sites. The inhibitory effects of FM-VP4 and cholesterol on each other were detectable after 1 h of incubation and increased with time. The extent of FM-VP4 inhibition of [3H]cholesterol accumulation was consistent whether FM-VP4 was co-incorporated into micelles or added separately in solution, suggesting that FM-VP4 does not elicit its effects through inhibition of cholesterol incorporation into micelles. In addition, pancreatic lipase activity ([3H]triolein hydrolysis) and p-glycoprotein (rhodamine 123 fluorescence) activity, were not affected by FM-VP4. CONCLUSIONS: In conclusion, FM-VP4 rapidly inhibits cholesterol accumulation within Caco-2 cell monolayers in a mode independent of pancreatic lipase activity, p-glycoprotein activity or cholesterol incorporation in micelles. (+info)
Fish oil containing phytosterol esters alters blood lipid profiles and left ventricle generation of thromboxane a(2) in adult guinea pigs.
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This study was designed to investigate the lipid-lowering ability of a novel dietary ingredient composed of phytosterols esterified to (n-3) polyunsaturated fatty acids (PUFA) [PS(n-3)]. Adult guinea pigs were fed a test diet supplemented with PS(n-3) (25 g/kg) and corn oil (CO, 5 g/kg), whereas the diet fed to control guinea pigs was supplemented with CO only (30 g/kg). Cholesterol was added to both diets (0.8 g/kg). After 3-4 wk of consuming the diets, serum total cholesterol (TC) and triacylglycerol (TAG) in the PS(n-3) group were 36 and 29% lower, respectively, than levels in controls (P < 0.05). The lower TC levels in the PS(n-3) group reflected a 38% reduction in non-HDL cholesterol (non-HDL-C), whereas the HDL-C concentration was unaffected. Analysis of cardiac left ventricle indicated that generation of the proaggregatory, arrhythmic eicosanoid, thromboxane A(2), was >60% lower in the PS(n-3)-supplemented guinea pigs than in CO controls (P < 0.001). This study demonstrates that the TAG-lowering and eicosanoid-modifying properties of the fish oil (n-3) PUFA are retained when they are provided in the diet in ester linkage with hypocholesterolemic phytosterols. (+info)
A single daily dose of soybean phytosterols in ground beef decreases serum total cholesterol and LDL cholesterol in young, mildly hypercholesterolemic men.
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BACKGROUND: Consumption of phytosterol-supplemented margarine lowers total plasma cholesterol (TC) and LDL-cholesterol concentrations in older middle-aged hypercholesterolemic individuals. The effects of incorporating phytosterols into lower-fat foods on the plasma lipids of young men at increased risk of developing cardiovascular disease have not been studied. OBJECTIVE: We tested the hypothesis that a single daily dose of soybean phytosterols added to ground beef will lower plasma TC and LDL-cholesterol concentrations in mildly hypercholesterolemic young men. DESIGN: In a triple-blind, 4-wk study, 34 male college students with elevated plasma TC (5.85 +/- 0.70 mmol/L), LDL cholesterol (4.02 +/- 0.60 mmol/L), and TC:HDL cholesterol (5.5 +/- 1.2) were randomly assigned to the control (ground beef alone) or treatment (ground beef with 2.7 g of phytosterols) group. The phytosterol mixture was two-thirds esterified and one-third nonesterified and consisted of beta-sitosterol (48%), campesterol (27%), and stigmasterol (21%). RESULTS: Consumption of phytosterol-supplemented ground beef lowered plasma TC and LDL-cholesterol concentrations and TC:HDL cholesterol from baseline by 9.3%, 14.6%, and 9.1%, respectively (P < 0.001). The LDL particle size did not change, suggesting that the decrease was primarily of particle number. The decreases were similar in subjects with (n = 8) and without (n = 9) a family history of premature cardiovascular disease. No significant changes were found in the control group. CONCLUSION: Phytosterol-supplemented ground beef effectively lowers plasma TC and LDL cholesterol and has the potential to become a functional food to help reduce the risk of cardiovascular disease. (+info)
Serum plant sterols and biliary cholesterol secretion in humans: studies with ursodeoxycholic acid.
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Ratios of cholestanol, campesterol, and sitosterol to cholesterol in serum are known to reflect cholesterol absorption efficiency. Here, a possible link between these ratios and biliary secretion rates of cholesterol was investigated. Biliary lipid secretion rates and serum sterols were determined in 13 patients with gallstones. Seven were treated with ursodeoxycholic acid (UDCA) (1,000 mg/d). Serum cholesterol and non-cholesterol sterols were also measured in a cross over study in 20 healthy volunteers, who received either placebo or UDCA (750 mg/d). Biliary cholesterol secretion was significantly lower, whereas the non-cholesterol sterols and their ratio to cholesterol were higher in patients with gallstones treated with UDCA. A highly significant negative linear correlation between the ratios of non-cholesterol sterols to cholesterol and biliary cholesterol secretion was observed. In volunteers, administration of UDCA for 4 weeks was followed by a significant increase in non-cholesterol sterols and their ratios. Even 4 weeks after discontinuing UDCA administration, campesterol and sitosterol were still significantly higher than pretreatment levels, which was also true for the campesterol-cholesterol ratio after 8 weeks. The results suggest that the ratios of cholestanol, campesterol, and sitosterol to cholesterol can be used as indicators of changes in biliary cholesterol secretion rates. (+info)