Increase in neutral cholesteryl ester hydrolase activity produced by extralysosomal hydrolysis of high-density lipoprotein cholesteryl esters in rat hepatoma cells (H-35)

Shimada, Akihiko; Tamai, Toshitaka; Oida, Koji; Takahashi, Sadao; Suzuki, Jinya; Nakai, Tsuguhiko; Miyabo, Susumu

doi:10.1016/0005-2760(94)90101-5

Cited by 26 publications

(26 citation statements)

References 46 publications

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“…Total plasma cholesterol (TPC) concentration was determined by a micro enzymatic method as described earlier ( 17 ). In brief, approximately 20 g of cholesterol was injected onto a fastprotein liquid chromatography system (Superose 6 HR 10/30 column, Amersham Biosciences) with online mixing of the column effl uent with enzymatic reagent (Cholesterol Liquid Stable, and LDLs are taken up by the endocytic pathway and the associated CEs are hydrolyzed within the acidic lysosomal compartment by acid CE hydrolase (CEH), CEs associated with HDLs enter the hepatocyte by selective uptake pathway via scavenger receptor BI (SR-BI) and hydrolysis of HDLCEs is extra lysosomal and catalyzed by a neutral CEH ( 8 ).…”

Section: Total Plasma Cholesterol and Cholesterol Distribution Among mentioning

confidence: 99%

Liver-specific transgenic expression of cholesteryl ester hydrolase reduces atherosclerosis in Ldlr−/− mice

Bie

Wang

Yuan

et al. 2014

Journal of Lipid Research

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Section: Total Plasma Cholesterol and Cholesterol Distribution Among mentioning

confidence: 99%

Liver-specific transgenic expression of cholesteryl ester hydrolase reduces atherosclerosis in Ldlr−/− mice

Bie

Wang

Yuan

et al. 2014

Journal of Lipid Research

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“…After 24 h, medium was replaced Greater than 80% of cholesterol associated with HDL is present as CEs and intracellular hydrolysis is required to make FC available for either secretion into the bile or for the synthesis of bile acids. Furthermore, Sampson et al showed that FC entering the hepatocytes from HDL also undergoes esterifi cation ( 6 ), and CEs thus generated are hydrolyzed in a nonacidic compartment ( 7 ). Despite the obvious "need" for intracellular, and probably neutral, hydrolysis of HDL-derived CEs, the identity of the enzyme responsible for this hydrolysis remains elusive.…”

Section: Bile Acid Synthesis In Primary Hepatocytesmentioning

confidence: 99%

Cooperation between hepatic cholesteryl ester hydrolase and scavenger receptor BI for hydrolysis of HDL-CE

Yuan

Bie

Wang

et al. 2013

Journal of Lipid Research

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This article is available online at http://www.jlr.org synthesized, results in its accumulation within the body leading to pathological consequences. Under homeostatic conditions, excess cholesterol accumulated in the peripheral tissues, e.g., arterial wall-associated macrophages, is returned back to the liver via high density lipoprotein (HDL). Liver plays a central role in the regulation of plasma cholesterol concentrations, as it is not only the major site for cholesterol synthesis and secretion of lipoproteins into blood, but it is also the sole organ able to remove cholesterol from the body. In species that do or do not express cholesteryl ester transfer protein (CETP), scavenger receptor BI (SR-BI)-mediated HDL uptake by liver represents the major mechanism for clearance of HDL-cholesterol (HDL-C) and cholesteryl esters (CEs).Hepatic SR-BI facilitates selective cholesterol uptake from HDL particles in which HDL-C as well as CEs are directly transferred to the cells without internalization and hydrolytic disassembly of the HDL particles. Free or unesterifi ed cholesterol (FC) from HDL delivered via SR-BI is thought to be directly secreted into bile without entering the hepatic metabolic pool ( 1, 2 ). Hepatic SR-BI thus regulates plasma HDL-C levels as well as the utilization of this cholesterol for biliary secretion ( 3 ). Pieters et al. ( 4 ) demonstrated that selective uptake of HDL-cholesteryl esters (HDL-CEs) is effi ciently coupled to bile acid synthesis. However, based on unchanged bile acid pool size and composition as well as fecal bile acid excretion in SR-BI Multiple pathways are involved in maintaining wholebody cholesterol homeostasis in adult organisms for which intestinal cholesterol absorption and endogenous cholesterol biosynthesis must be balanced with biliary cholesterol and bile acid secretion. Endogenous synthesis of cholesterol, which occurs predominantly in the liver, is tightly regulated by cholesterol levels. Abbreviations: AdCEH, cholesteryl ester hydrolase expressing adenovirus; AdLacZ, ␤ galactosidase expressing adenovirus; AdSR-BI, scavenger receptor BI expressing adenovirus; CE, cholesteryl ester; CEH, cholesteryl ester hydrolase; CETP, cholesteryl ester transfer protein; FC, free or unesterifi ed cholesterol; HDL-C, HDL-cholesterol; HDL-CE, HDL cholesteryl ester; MOI, multiplicity of infection; NPC1, Niemann-Pick C1; RCT, reverse cholesterol transport; SR-BI, scavenger receptor BI .

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“…Although the details of this internalization step are not clear, in some manner cholesteryl ester from the HDL particle is selectively translocated into the cell while the protein component of the lipoprotein is left in the extracellular fluid to be either reutilized or degraded in the kidney (12)(13)(14). This cholesteryl ester is then hydrolyzed by a neutral cholesteryl ester esterase, and the unesterified sterol is delivered directly into the metabolically active pools in the cell (15,16). Importantly, this intracellular pathway bypasses the acidification step involved in the LDLR-dependent, clathrin-coated pit pathway.…”

mentioning

confidence: 99%

Cholesterol substrate pools and steroid hormone levels are normal in the face of mutational inactivation of NPC1 protein

Xie

Richardson

Turley

et al. 2006

Journal of Lipid Research

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Mutational inactivation of NPC1 largely blocks the movement of LDL-derived cholesterol from the lysosome to the metabolically active, cytosolic pool of sterol that is the substrate for steroid hormone production. Such a block might, in theory, lead to deficiencies in circulating levels of testosterone, progesterone, and corticosterone. However, there are at least two other sources for cellular cholesterol, de novo synthesis and scavenger receptor class B type I-mediated uptake of HDL cholesteryl ester (CE). In this study, we measured the rates of net cholesterol acquisition by these three pathways in the adrenal, ovary, and testis. In all three organs, the majority (81-98%) of cholesterol acquisition came from the selective uptake of CE from HDL and de novo synthesis. Furthermore, in the npc1 2/2 mouse, the cytosolic storage pool of CE in a tissue such as the adrenal remained constant (z25 mg/g). As a result of these alternative pathways, the plasma concentrations of testosterone (3.5 vs. 2.5 ng/ml), progesterone (8.5 vs. 6.7 ng/ml), and corticosterone (391 vs. 134 ng/ml) were either the same or elevated in the npc1 2/2 mouse, compared with the control animal.Thus, impairment of cholesterol acquisition through the NPC1-dependent, clathrin-coated pit pathway did not limit the availability of cholesterol substrate for steroid hormone synthesis in the steroidogenic cells. Essentially all cells acquire cholesterol primarily through de novo synthesis (1-3). In addition, at least three different proteins located in the plasma membrane are recognized that can also bring about the net transfer of sterol from the extracellular environment into the metabolically active pools of cholesterol within these cells. The first of these, the LDL receptor (LDLR), can take up lipoproteins that contain one of two ligands, apolipoprotein B 100 (apoB 100 ) or apoE, and these include LDL and the remnants of both VLDL and chylomicrons (4, 5). This transport process involves binding of the ligand to the receptor, clustering of the bound lipoproteins into clathrin-coated pits, and finally, internalization of these particles into the endosomal/ lysosomal compartment of the cell (6). There, acidification leads to a change in the configuration of the binding site on the LDLR, release of the lipoprotein, and ultimately, hydrolysis of the cholesteryl ester (CE) contained in these particles by an acidic cholesteryl ester esterase, i.e., acid lipase (7-9). Thus, this LDLR-dependent endocytosis results in the uptake of the cholesterol, both esterified and unesterified, carried in particles like LDL, and deposits it as unesterified sterol in the endosomal compartment of the cell.The second plasma membrane protein, scavenger receptor class B type I (SR-BI), binds lipoproteins containing apoAI such as HDL, and then processes these particles through a very different pathway (10,11). Although the details of this internalization step are not clear, in some manner cholesteryl ester from the HDL particle is selectively translocated into the cell ...

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Increase in neutral cholesteryl ester hydrolase activity produced by extralysosomal hydrolysis of high-density lipoprotein cholesteryl esters in rat hepatoma cells (H-35)

Cited by 26 publications

References 46 publications

Liver-specific transgenic expression of cholesteryl ester hydrolase reduces atherosclerosis in Ldlr−/− mice

Liver-specific transgenic expression of cholesteryl ester hydrolase reduces atherosclerosis in Ldlr−/− mice

Cooperation between hepatic cholesteryl ester hydrolase and scavenger receptor BI for hydrolysis of HDL-CE

Cholesterol substrate pools and steroid hormone levels are normal in the face of mutational inactivation of NPC1 protein

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