Effects of Phosphatidylcholine/Phosphatidylethanolamine Composition in Cholesteryl Ester–Micellar Substrates on Neutral Cholesterol Esterase Activity

Chiba, Tsuyoshi; Uematsu, Shogo; Sawamura, Fusae; Sugawara, Mika; Tomita, Isao; Kajiyama, Fumiyasu; Tomita, Takako

doi:10.1006/abio.1998.3071

Cited by 5 publications

(2 citation statements)

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“…In previous assays, cholesterol oleate (CO) has been used in the form of an emulsion stabilized by gum arabic (GA) (14), dispersed with phosphatidylcholine (PC) in glycerol (15), dispersed in PC and sodium taurocholate (16), dispersed in PC/phosphatidylethanolamine liposomes (17), or emulsified with PC/phosphatidylinositol (PI; 3:1, w/w) (12). It turns out that, in addition to the buffer composition and pH, the hydrolysis of cholesteryl esters by cholesteryl ester-hydrolyzing enzymes depends strongly on the mode of organization of the lipid substrate present in interfacial structures, such as monolayers, micelles, liposomal dispersions, or oil-in-water emulsions.…”

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confidence: 99%

Continuous monitoring of cholesterol oleate hydrolysis by hormone-sensitive lipase and other cholesterol esterases

Ali

Carrière

Verger

et al. 2005

Journal of Lipid Research

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Hormone-sensitive lipase (HSL) contributes importantly to the hydrolysis of cholesteryl ester in steroidogenic tissues, releasing the cholesterol required for adrenal steroidogenesis. HSL has broad substrate specificity, because it hydrolyzes triacylglycerols (TAGs), diacylglycerols, monoacylglycerols, and cholesteryl esters. In this study, we developed a specific cholesterol esterase assay using cholesterol oleate (CO) dispersed in phosphatidylcholine and gum arabic by sonication. To continuously monitor the hydrolysis of CO by HSL, we used the pH-stat technique. For the sake of comparison, the hydrolysis of CO dispersion was also tested using other cholesteryl ester-hydrolyzing enzymes. The specific activities measured on CO were found to be 18, 100, 27, and 3 mol/min/mg for HSL, cholesterol esterase from Pseudomonas species, Candida rugosa lipase-3, and cholesterol esterase from bovine pancreas, respectively. The activity of HSL on CO is ‫ف‬ 4-to 5-fold higher than on long-chain TAGs. In contrast, with all other enzymes tested, the rates of TAG hydrolysis were higher than those of CO hydrolysis. The relatively higher turnover of HSL on CO observed in vitro adds further molecular insight on the physiological importance of HSL in cholesteryl ester catabolism in vivo. Thus, HSL could be considered more as a cholesteryl ester hydrolase than as a TAG lipase. FFAs are an important source of energy in mammals. Hormone-sensitive lipase (HSL) is thought to play a crucial role in the mobilization of FFAs from the triacylglycerols (TAGs) stored in adipocytes (for review, see 1). In vivo, HSL is activated by phosphorylation via cAMP-dependent kinase in response to various lipolytic hormones, such as catecholamines. Phosphorylation of HSL leads to its translocation from the cytoplasm to the lipid droplet (2). Insulin acts as an antilipolytic hormone by phosphorylating and activating phosphodiesterase 3B, which hydrolyzes cAMP and thus reduces the hydrolysis of TAG (1) by HSL. In addition to adipocytes, HSL is expressed in other tissues (3), including skeletal muscle, heart, brain, pancreatic ␤ cells, adrenal gland, ovaries, testes, and macrophages (1).HSL also plays an important role in the mobilization of cholesterol from cholesteryl ester. Cholesteryl esters provide the cholesterol required for steroid synthesis in steroidogenic tissues, such as the adrenal cortex. The level of cholesteryl ester hydrolase activity in the adrenals of HSLnull mice has been found to be reduced by more than 98% compared with that in wild-type mice, which suggests that HSL is mainly responsible for the hydrolysis of most of the cholesteryl esters present in this tissue and that it is involved in the intracellular processing of the cholesterol required for adrenal steroidogenesis (4, 5). Furthermore, evidence has been presented in various studies (6, 7) that HSL contributes importantly to the hydrolysis of most of the cholesteryl esters present in macrophage foam cells. However, Contreras (8) has reported that cholesteryl esters from...

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confidence: 99%

Continuous monitoring of cholesterol oleate hydrolysis by hormone-sensitive lipase and other cholesterol esterases

Ali

Carrière

Verger

et al. 2005

Journal of Lipid Research

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“…We observed no reduction of pancreatic lipase activity in the presence of FM-VP4 (50). Some of the lipolytic products of the major pancreatic enzymes, including cholesterol, are only minimally soluble in aqueous systems and depend on the solubilizing properties of bile salts (10,12,13,36,38,53). When phospholipids or monoacylglycerides, in addition to bile salts, are present, cholesterol is solubilized into a mixed micelle solution and can be readily absorbed (10,12,13,36,38,53).…”

Section: Pharmacology Cell Culture Studiesmentioning

confidence: 99%

Development of Novel Water‐Soluble Phytostanol Analogs: Disodium Ascorbyl Phytostanyl Phosphates (FM‐VP4): Preclinical Pharmacology, Pharmacokinetics and Toxicology

Ng¹,

Lukić²,

Pritchard

2003

Cardiovascular Drug Reviews

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FM-VP4 is a novel inhibitor of cholesterol absorption that has lipid lowering and body weight reducing properties. In vitro and in vivo studies were performed to investigate the lipid-lowering effects, mechanism of action, pharmacokinetics, and toxicity of FM-VP4. FM-VP4 decreased cholesterol accumulation in Caco-2 cells by approximately 50%; its activity appeared to be independent of pancreatic lipase, p-glycoprotein, or cholesterol incorporation in micelles. In animal studies, FM-VP4 was added to the diet or drinking water and the following results were obtained. In gerbils 2% FM-VP4 produced mean 56 and 53% reduction in total cholesterol (TC) after 4 and 8 weeks, respectively. This reduction was entirely due to the loss of the low-density lipoprotein (LDL) pool, which was reduced to undetectable levels at either time point. At 8 weeks, high-density lipoprotein (HDL) concentration had risen by a mean of 34% whereas total triglyceride (TG) concentrations had decreased by a mean of 60%. FM-VP4 also had a profound effect on body weight in these animals. At 8 weeks, the mean body weight was in the 4% FM-VP4 treatment group 25% lower than in the control group. No hepatic or renal toxicity was associated with these changes. In Apo E-deficient mice, after 4-and 8-week treatments FM-VP4 caused a significant decrease in both TC and TG concentrations compared to controls. After 12 weeks, the areas of atherosclerotic lesion involvement in the aortic roots were decreased by a mean of 80% in the 0.5, 1, and 2% FM-VP4 treatment groups compared to controls. Taken together, these results suggest that FM-VP4 is a potential new drug with lipid-lowering and weight loss potential, without apparent toxicity.

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Cholesterol Ester Hydrolases

Grogan

2002

Wiley Encyclopedia of Molecular Medicine

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Effects of Phosphatidylcholine/Phosphatidylethanolamine Composition in Cholesteryl Ester–Micellar Substrates on Neutral Cholesterol Esterase Activity

Cited by 5 publications

References 21 publications

Continuous monitoring of cholesterol oleate hydrolysis by hormone-sensitive lipase and other cholesterol esterases

Continuous monitoring of cholesterol oleate hydrolysis by hormone-sensitive lipase and other cholesterol esterases

Development of Novel Water‐Soluble Phytostanol Analogs: Disodium Ascorbyl Phytostanyl Phosphates (FM‐VP4): Preclinical Pharmacology, Pharmacokinetics and Toxicology

Cholesterol Ester Hydrolases

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