The Experts below are selected from a list of 204 Experts worldwide ranked by ideXlab platform
Edward A. Fisher - One of the best experts on this subject based on the ideXlab platform.
-
The effects of varying the expression of a neutral CholEsteryl Ester hydrolase on the turnover of CholEsteryl Ester in rat hepatoma cells.
The Journal of biological chemistry, 1993Co-Authors: R Zolfaghari, J M Glick, Edward A. FisherAbstract:Abstract A neutral bile salt-dependent CholEsteryl Ester hydrolase (CEH) in rat liver has been shown to be indistinguishable from the pancreatic CEH by a number of criteria (Harrison, E. H. (1988) Biochim. Biophys. Acta 963, 28-34; Zolfaghari, R., Harrison, E. H., Ross, A. C., and Fisher, E. A. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 6913-6919; Camulli, E. D., Linke, M. J., Brockman, H. L., and Hui, D. Y. (1989) Biochim. Biophys. Acta 1005, 177-182). The rat hepatoma cell line Fu5AH, which lacks this particular CEH activity, was stably transfected with the cDNA of rat pancreatic CEH, and the effects on cholEsterol and CholEsteryl Ester metabolism in clones with varying levels of CEH expression determined. In spite of significant amounts of intracellular enzyme protein demonstrated by WEstern blotting, in cell lysates there was a consistently low level of catalytic activity, and in cultured cells there was no evidence that CEH served as an effective intracellular CholEsteryl Ester hydrolase or synthase. In contrast, the catalytic activity of the secreted enzyme was relatively higher and there was a small, but significant, increase in the ability of high density lipoprotein (added to the medium) to promote the clearance of CholEsteryl Ester from cells secreting high levels of CEH. Overall, these results suggest that in the liver, intracellular CEH does not significantly affect the turnover of CholEsteryl Esters and warrant future studies focusing on the function of the secreted enzyme. For example, secreted CEH may modify lipoproteins and affect their interactions with cells.
Susumu Miyabo - One of the best experts on this subject based on the ideXlab platform.
-
Increase in neutral CholEsteryl Ester hydrolase activity produced by extralysosomal hydrolysis of high-density lipoprotein CholEsteryl Esters in rat hepatoma cells (H-35)
Biochimica et Biophysica Acta (BBA) Lipids and Lipid Metabolism, 1994Co-Authors: Toshitaka Tamai, Koji Oida, Jinya Suzuki, Tsuguhiko Nakai, Sadao Takahashi, Susumu MiyaboAbstract:The metabolism of high-density lipoprotein-associated CholEsteryl Esters (HDL-CE) in liver cells is not well understood. We studied the possible role of lysosomal and extralysosomal pathways on such metabolism by measuring the uptake and hydrolysis of HDL-CE in H-35 rat hepatoma cells. Incubation of cells with [3H]CholEsteryl Ester-labeled HDL led to the intracellular accumulation of both3H-free cholEsterol and [3H]CholEsteryl Ester. The ratio of3H-free cholEsterol/[3H]CholEsteryl Ester increased with an increase in incubation time even in the presence of chloroquine. Because chloroquine did not inhibit the conversion of CholEsteryl Ester to free cholEsterol, the hydrolysis of HDL-CE may have been catalyzed by an extralysosomal enzyme, perhaps by neutral CholEsteryl Ester hydrolase (NCEH). When we incubated cells with increasing concentrations of HDL, NCEH activity increased. This increase in enzyme activity was not inhibited by the addition of chloroquine. A complex of dimyristoylphosphatidylcholine (DMPC)/apo HDL/CholEsteryl Ester enhanced the activity as well as native HDL. Neither the DMPC/apo HDL nor the DMPC/cholEsteryI Ester complex affected the activity, suggesting that apo HDL may be required for the uptake of HDL-CE. The present study demonstrated that the extralysosomal hydrolysis by NCEH is operating in the metabolism of HDL-CE in hepatoma cells. © 1994.
R Zolfaghari - One of the best experts on this subject based on the ideXlab platform.
-
The effects of varying the expression of a neutral CholEsteryl Ester hydrolase on the turnover of CholEsteryl Ester in rat hepatoma cells.
The Journal of biological chemistry, 1993Co-Authors: R Zolfaghari, J M Glick, Edward A. FisherAbstract:Abstract A neutral bile salt-dependent CholEsteryl Ester hydrolase (CEH) in rat liver has been shown to be indistinguishable from the pancreatic CEH by a number of criteria (Harrison, E. H. (1988) Biochim. Biophys. Acta 963, 28-34; Zolfaghari, R., Harrison, E. H., Ross, A. C., and Fisher, E. A. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 6913-6919; Camulli, E. D., Linke, M. J., Brockman, H. L., and Hui, D. Y. (1989) Biochim. Biophys. Acta 1005, 177-182). The rat hepatoma cell line Fu5AH, which lacks this particular CEH activity, was stably transfected with the cDNA of rat pancreatic CEH, and the effects on cholEsterol and CholEsteryl Ester metabolism in clones with varying levels of CEH expression determined. In spite of significant amounts of intracellular enzyme protein demonstrated by WEstern blotting, in cell lysates there was a consistently low level of catalytic activity, and in cultured cells there was no evidence that CEH served as an effective intracellular CholEsteryl Ester hydrolase or synthase. In contrast, the catalytic activity of the secreted enzyme was relatively higher and there was a small, but significant, increase in the ability of high density lipoprotein (added to the medium) to promote the clearance of CholEsteryl Ester from cells secreting high levels of CEH. Overall, these results suggest that in the liver, intracellular CEH does not significantly affect the turnover of CholEsteryl Esters and warrant future studies focusing on the function of the secreted enzyme. For example, secreted CEH may modify lipoproteins and affect their interactions with cells.
Le D Goff - One of the best experts on this subject based on the ideXlab platform.
-
evaluation of CholEsteryl Ester transfer in the seminiferous tubule cells of immature rats in vivo and in vitro
Reproduction, 2000Co-Authors: M Fofana, Carine Travert, Serge Carreau, Le D GoffAbstract:Sertoli cells and germ cells are separated from the interstitial blood capillaries by an extracellular matrix and the peritubular cells, which constitute a barrier to the movement of plasma lipoproteins. The present study was undertaken to evaluate in vivo and in vitro the high density lipoprotein (HDL) CholEsteryl Ester transfer from plasma to seminiferous tubule cells in the testis of 30-day-old rats. Firstly, the transfer of HDL CholEsteryl oleate from plasma to testicular compartments was evaluated and, secondly, the role of apolipoproteins A-I and E in the uptake of CholEsteryl Ester by Sertoli cells was investigated. At 2 h after the administration of HDL reconstituted with [ 3 H]CholEsteryl Ester, dimyristoyl phosphatidylcholine and apolipoproteins, the tissue space in the interstitial cells (740 ± 60 µl g ‐1 cell protein) was fourfold higher than that in the seminiferous tubule cells (170 ± 10 µl g ‐1 ). Sertoli cells were isolated and incubated with [ 3 H]CholEsteryl Ester HDL reconstituted with apolipoprotein A-I or E to evaluate the mechanisms of CholEsteryl Ester influx. At the same apolipoprotein concentration (50 µg apolipoprotein ml ‐1 medium), the uptake of [ 3 H]CholEsteryl oleate from phospholipid‐apolipoprotein E vesicles was twofold higher than that with phospholipid‐apolipoprotein A-I vesicles. The presence of heparin reduced the uptake of CholEsteryl Ester from apolipoprotein E vesicles but not with apolipoprotein A-I vesicles, indicating that uptake of apolipoprotein A-I vesicles via a secretion of apolipoprotein E by the cells themselves was not involved. These results demonstrate that plasma lipoprotein cholEsterol is able to cross the testis lamina propria and that Sertoli cells take up CholEsteryl Ester for seminiferous tubule cell metabolism mainly via an apolipoprotein E pathway.
Anatol Kontush - One of the best experts on this subject based on the ideXlab platform.
-
CholEsteryl Ester transfer protein at the heart of the action of lipid modulating therapy with statins fibrates niacin and CholEsteryl Ester transfer protein inhibitors
European Heart Journal, 2010Co-Authors: John M Chapman, Wilfried Le Goff, Maryse Guerin, Anatol KontushAbstract:Subnormal plasma levels of high-density lipoprotein cholEsterol (HDL-C) constitute a major cardiovascular risk factor; raising low HDL-C levels may therefore reduce the residual cardiovascular risk that frequently presents in dyslipidaemic subjects despite statin therapy. CholEsteryl Ester transfer protein (CETP), a key modulator not only of the intravascular metabolism of HDL and apolipoprotein (apo) A-I but also of triglyceride (TG)-rich particles and low-density lipoprotein (LDL), mediates the transfer of CholEsteryl Esters from HDL to pro-atherogenic apoB-lipoproteins, with heterotransfer of TG mainly from very low-density lipoprotein to HDL. CholEsteryl Ester transfer protein activity is elevated in the dyslipidaemias of metabolic disease involving insulin resistance and moderate to marked hypertriglyceridaemia, and is intimately associated with premature atherosclerosis and high cardiovascular risk. CholEsteryl Ester transfer protein inhibition therefore presents a preferential target for elevation of HDL-C and reduction in atherosclerosis. This review appraises recent evidence for a central role of CETP in the action of current lipid-modulating agents with HDL-raising potential, i.e. statins, fibrates, and niacin, and compares their mechanisms of action with those of pharmacological agents under development which directly inhibit CETP. New CETP inhibitors, such as dalcetrapib and anacetrapib, are targeted to normalize HDL/apoA-I levels and anti-atherogenic activities of HDL particles. Further studies of these CETP inhibitors, in particular in long-term, large-scale outcome trials, will provide essential information on their safety and efficacy in reducing residual cardiovascular risk.