Apolipoprotein E Is the Major Physiological Activator of Lecithin−Cholesterol Acyltransferase (LCAT) on Apolipoprotein B Lipoproteins

Zhao, Yue; Thorngate, Fayanne E.; Weisgraber, Karl H.; Williams, David L.; Parks, John S.

doi:10.1021/bi0481489

Cited by 48 publications

(36 citation statements)

References 49 publications

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“…In addition, removal of the apoE resulted in a loss of ability of HDL to promote cholesteryl ester accumulation suggesting that apoE may play a key role. Other studies suggest that apoE has an important role as an LCAT activator in mouse apoB lipoproteins [275]. In an x-ray crystal model of apoE bound to phospholipids, it has been suggested that apoE molecule was folded into half in a belt-like manner around a spheroidal phospholipid molecule, forming a circular horseshoe two helices thick and one helix wide but not a complete belt [276].…”

Section: Abcg1mentioning

confidence: 99%

Recent advances in physiological lipoprotein metabolism

Ramasamy

2014

Clinical Chemistry and Laboratory Medicine (CCLM)

188

159

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Abstract:Research into lipoprotein metabolism has developed because understanding lipoprotein metabolism has important clinical indications. Lipoproteins are risk factors for cardiovascular disease. Recent advances include the identification of factors in the synthesis and secretion of triglyceride rich lipoproteins, chylomicrons (CM) and very low density lipoproteins (VLDL). These included the identification of microsomal transfer protein, the cotranslational targeting of apoproteinB (apoB) for degradation regulated by the availability of lipids, and the characterization of transport vesicles transporting primordial apoB containing particles to the Golgi. The lipase maturation factor 1, glycosylphosphatidylinositol-anchored high density lipoprotein binding protein 1 and an angiopoietin-like protein play a role in lipoprotein lipase (LPL)-mediated hydrolysis of secreted CMs and VLDL so that the right amount of fatty acid is delivered to the right tissue at the right time. Expression of the low density lipoprotein (LDL) receptor is regulated at both transcriptional and posttranscriptional level. Proprotein convertase subtilisin/ kexin type 9 (PCSK9) has a pivotal role in the degradation of LDL receptor. Plasma remnant lipoproteins bind to specific receptors in the liver, the LDL receptor, VLDL receptor and LDL receptor-like proteins prior to removal from the plasma. Reverse cholesterol transport occurs when lipid free apoAI recruits cholesterol and phospholipid to assemble high density lipoprotein (HDL) particles. The discovery of ABC transporters (ABCA1 and ABCG1) and scavenger receptor class B type I (SR-BI) provided further information on the biogenesis of HDL. In humans HDLcholesterol can be returned to the liver either by direct uptake by SR-BI or through cholesteryl ester transfer protein exchange of cholesteryl ester for triglycerides in apoB lipoproteins, followed by hepatic uptake of apoB containing particles. Cholesterol content in cells is regulated by several transcription factors, including the liver X receptor and sterol regulatory element binding protein. This review summarizes recent advances in knowledge of the molecular mechanisms regulating lipoprotein metabolism.Keywords: ABCA1; angiopoietin-like proteins; apoC; apoAI; apolipoprotein E (apoE); cholesterol ester transfer protein; chylomicron; LDL receptor; lecithin cholesterol acyl transferase; lipoprotein(a); lipoprotein lipase; microsomal transfer protein; propertin convertase subtilisin/ kexin type 9; SR-BI; phospholipid transfer protein; very low density lipoproteins (VLDL). Abstract 1695

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Section: Abcg1mentioning

confidence: 99%

Recent advances in physiological lipoprotein metabolism

Ramasamy

2014

Clinical Chemistry and Laboratory Medicine (CCLM)

188

159

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“…ApoE at high levels restricts VLDL lipolysis, in part by displacing the lipoprotein lipase activator apoprotein CII from the particle (8). ApoA-I, the premier activator of LCAT, is much less efficient on large HDL particles and apoB-containing lipoproteins where apoE functions as the LCAT activator (9,10). ApoE may also influence the activity of hepatic lipase and cholesteryl ester transfer protein (CETP) (11).…”

Section: Apoe and Plasma Lipoprotein Homeostasismentioning

confidence: 99%

Apoprotein E as a lipid transport and signaling protein in the blood, liver, and artery wall

Getz

Reardon

2009

Journal of Lipid Research

240

155

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Apoprotein E (apoE) is synthesized by a number of tissues including the liver, brain, adipose tissue, and artery wall. The majority of apoE is found in the plasma associated with specific lipoprotein subclasses and is derived primarily from the liver. However the fact that apoE expression is sustained in nonhepatic tissues suggests that the local production must have some unique functional attribute. ApoE is involved in many steps in lipid and lipoprotein homeostasis, for the triglyceride-rich lipoproteins and for HDL. ApoE is also important for lipid homeostasis in the brain, artery wall, and adipose tissue through its synthesis by glial cells, adipocytes, and macrophages. In addition, nonlipid related functions have also been attributed to apoE, including effects on immune response and inflammation, oxidation, and smooth muscle proliferation and migration. Some of these effects have been shown to be dependent upon different domains of the protein, different concentrations, and lipidation state. Thus, this multifunctional protein impacts normal and pathophysiology at multiple levels.-Getz, G. S., and C. A. Reardon. Apoprotein E as a lipid transport and signaling protein in the blood, liver, and ar tery wall.

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“…Plasma LCAT cholesterol esterification rate (CER) was determined using a modification of the Stokke and Norum procedure [5][6][7] . Briefly, a pooled plasma sample (200 L) was incubated with BSA solution containing 3 10 6 dpm of 3 H-cholesterol on ice overnight.…”

Section: Endogenous Lcat Assaysmentioning

confidence: 99%

“…Type 2 diabetes is an important risk factor for the development of cardiovascular diseases (CVD) 6) and recently, blood glucose level management has been shown to be important in avoiding microvascular and macrovascular complication of diabetes 7,8) . Oral anti-diabetic sulfonylurea agents (SUAs) have been widely used to improve glycemic control.…”

Section: Introductionmentioning

confidence: 99%