Secretion of very low density lipoproteins enriched in cholesteryl esters by cultured rat hepatocytes during simulation of intracellular cholesterol esterification

Drevon, Christian A.; Engelhorn, Sheldon C.; Steinberg, Daniel

doi:10.1016/s0022-2275(20)34767-2

Cited by 95 publications

(2 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ACAT2 plays an important role in the absorption of cholesterol in the small intestine, before cholesterol is incorporated into CM . In the liver, this enzyme is partially responsible for the assembly of very low-density lipoproteins (VLDL) prior to secretion into the blood . TG-rich VLDL particles derived from the liver are transformed into cholesterol-rich LDL after the removal of their TG by peripheral tissues.…”

Section: Classification Of Cholesterol-lowering Nutraceuticals and Foodsmentioning

confidence: 99%

Cholesterol-Lowering Nutraceuticals and Functional Foods

Chen

Jiao

Ying

2008

J. Agric. Food Chem.

234

173

View full text Add to dashboard Cite

Epidemiological studies have demonstrated that elevated levels of plasma total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) are the major risk factors for coronary heart disease (CHD), whereas high concentrations of plasma high-density lipoprotein cholesterol (HDL-C) and a low ratio of TC to HDL-C are protective against CHD. A relationship between plasma TC and the risk of CHD is well established at concentrations above 240 mg/dL. In addition to the use of three main classes of cholesterol-lowering medications, including HMG-CoA reductase inhibitors, anion-exchange resins, and fibrates, a nutritionally balanced diet that reduces saturated fat and cholesterol intake has traditionally been the first goal of dietary therapy in lowering plasma TC. In recent years, nutraceuticals and functional foods have attracted much interest as possible alternative therapies for lowering plasma TC, especially for hypercholesterolemia patients, whose blood cholesterol level is marginally high (200-240 mg/dL) but not high enough to warrant the prescription of cholesterol-lowering medications. This review summarizes the findings of recent studies on the production, application, efficacy, and mechanisms of popular cholesterol-lowering nutraceuticals and functional foods.

show abstract

Section: Classification Of Cholesterol-lowering Nutraceuticals and Foodsmentioning

confidence: 99%

Cholesterol-Lowering Nutraceuticals and Functional Foods

Chen

Jiao

Ying

2008

J. Agric. Food Chem.

234

173

View full text Add to dashboard Cite

show abstract

“…and hepatic ACAT may modulate the cholesteryl ester composition of VLDL (Drevon et al, 1980). In adrenal gland and ovary, cholesteryl esters formed by ACAT are substrates stored for ultimate use in the synthesis of steroid hormones, and ACAT activity is regulated reciprocally with steroid hormone synthesis (Civen et al, 1984;Tavani et al, 1982).…”

mentioning

confidence: 99%

Chemical modification of acyl-CoA:cholesterol-O-acyltransferase. 1. Identification of acyl-CoA:cholesterol O-acyltransferase subtypes by differential diethyl pyrocarbonate sensitivity

Kinnunen¹,

DeMichele²,

Lange³

1988

Biochemistry

View full text Add to dashboard Cite

Acyl-CoA:cholesterol O-acyltransferase (EC 2.3.1.26) (ACAT) catalyzes the intracellular synthesis of cholesteryl esters from cholesterol and fatty acyl-CoA at neutral pH. Despite the probable pathophysiologic role of ACAT in vascular cholesteryl ester accumulation during atherogenesis, its mechanism of action and its regulation remain to be elucidated because the enzyme polypeptide has never been identified or purified. Present chemical modification results identify two distinct tissue types of ACAT, based on marked differences in reactivity of an active-site histidine residue toward diethyl pyrocarbonate (DEP) and acetic anhydride. The apparent Ki of the DEP-sensitive ACAT subtype, typified by aortic ACAT, was 40 microM, but the apparent Ki of the DEP-resistant ACAT subtype, typified by liver ACAT, was 1500 microM, indicating a 38-fold difference in sensitivity to DEP. Apparent Ki's of aortic and liver ACAT for inhibition by acetic anhydride were also discordant (less than 500 microM and greater than 5 mM, respectively). On the basis of the reversibility of inhibition by hydroxylamine, a neutral pKa for maximal modification, and acetic anhydride protection against DEP inactivation, DEP and acetic anhydride appear to modify a common histidine residue. Oleoyl-CoA provided partial protection against inactivation by DEP and acetic anhydride, suggesting that the modified histidine is at or near the active site of ACAT. Systematic investigation of ACAT activity from 14 different organs confirmed the existence of 2 subtypes of ACAT on the basis of their different reactivities toward DEP and acetic anhydride.(ABSTRACT TRUNCATED AT 250 WORDS)

show abstract

Dietary iron overload and induced lipid peroxidation are associated with impaired plasma lipid transport and hepatic sterol metabolism in rats

et al. 1999

View full text Add to dashboard Cite

Although hemochromatosis is characterized by dramatic morphological and functional alterations in the liver, little is known about the effects of an excess of iron on lipid metabolism. Therefore, we determined the effect of chronic iron overload on plasma lipid profile and lipoprotein composition, as well as on hepatic cholesterol metabolism and biliary sterol output. Rats administered a diet enriched with 3% iron carbonyl for 12 weeks displayed a 30-fold increase in iron (P F .0001) and a 5-fold rise in malondialdehyde (P F .001) in the liver. When compared with pair-fed controls, iron-overload rats showed a significant increase in triglycerides (P F .005), free cholesterol (P F .006), cholesteryl ester (P F .007), and high-density lipoprotein (HDL)-cholesterol (P F .003). Triglyceride and cholesteryl ester enrichment, protein depletion, size increase, and apolipoprotein composition alterations characterized the very low density lipoprotein (VLDL) and HDL particles of iron-overload rats. Assessment of the activity of intracellular key enzymes for cholesterol homeostasis in these rats disclosed a reduction in 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase (66%, P F .005) and cholesterol 7␣-hydroxylase (58%, P F .0004) with an increment of acyl-CoA: cholesterol acyltransferase (62%, P F .002). The lack of optimal enzymatic activity may be a result of marked membrane lipid peroxidation that brings about fluidity drop (P F .

show abstract

Secretion of very low density lipoproteins enriched in cholesteryl esters by cultured rat hepatocytes during simulation of intracellular cholesterol esterification

Cited by 95 publications

References 26 publications

Cholesterol-Lowering Nutraceuticals and Functional Foods

Cholesterol-Lowering Nutraceuticals and Functional Foods

Chemical modification of acyl-CoA:cholesterol-O-acyltransferase. 1. Identification of acyl-CoA:cholesterol O-acyltransferase subtypes by differential diethyl pyrocarbonate sensitivity

Dietary iron overload and induced lipid peroxidation are associated with impaired plasma lipid transport and hepatic sterol metabolism in rats

Contact Info

Product

Resources

About