Lecithin: Cholesterol Acyltransferase and Intravascular Cholesterol Transport

Marcel, Yves L.

doi:10.1016/b978-0-12-024919-0.50009-6

Cited by 70 publications

(23 citation statements)

References 182 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Paraoxonase is thought to be involved in the cleavage of lipid peroxides, among other substrates [50,51], and is therefore thought to have a critical part in HDL's ability to antagonize the biological activities of oxidized LDL [52]. LCAT, in contrast, can generate lyso-PtdCho by a transacylation of a sn-2 fatty acid from phosphatidylcholine to the 3-hydroxy group of cholesterol [53]. However, only LCAT could have contributed in our HDL oxidation assay owing to the lack of Ca# + , a critical cofactor for paraoxonase.…”

Section: Figure 6 Sb-222657 Prevents the Generation Of Oxidized Non-ementioning

confidence: 99%

Lipoprotein-associated phospholipase A2, platelet-activating factor acetylhydrolase, generates two bioactive products during the oxidation of low-density lipoprotein: use of a novel inhibitor

Macphee

Moores

Boyd

et al. 1999

Biochemical Journal

262

View full text Add to dashboard Cite

A novel and potent azetidinone inhibitor of the lipoprotein-associated phospholipase A2 (Lp-PLA2), i.e. platelet-activating factor acetylhydrolase, is described for the first time. This inhibitor, SB-222657 (Ki = 40±3 nM, kobs/[I] = 6.6×105 M-1·s-1), is inactive against paraoxonase, is a poor inhibitor of lecithin:cholesterol acyltransferase and has been used to investigate the role of Lp-PLA2 in the oxidative modification of lipoproteins. Although pretreatment with SB-222657 did not affect the kinetics of low-density lipoprotein (LDL) oxidation by Cu2+ or an azo free-radical generator as determined by assay of lipid hydroperoxides (LOOHs), conjugated dienes and thiobarbituric acid-reacting substances, in both cases it inhibited the elevation in lysophosphatidylcholine content. Moreover, the significantly increased monocyte chemoattractant activity found in a non-esterified fatty acid fraction from LDL oxidized by Cu2+ was also prevented by pretreatment with SB-222657, with an IC50 value of 5.0±0.4 nM. The less potent diastereoisomer of SB-222657, SB-223777 (Ki = 6.3±0.5 µM, kobs/[I] = 1.6×104 M-1·s-1), was found to be significantly less active in both assays. Thus, in addition to generating lysophosphatidylcholine, a known biologically active lipid, these results demonstrate that Lp-PLA2 is capable of generating oxidized non-esterified fatty acid moieties that are also bioactive. These findings are consistent with our proposal that Lp-PLA2 has a predominantly pro-inflammatory role in atherogenesis. Finally, similar studies have demonstrated that a different situation exists during the oxidation of high-density lipoprotein, with enzyme(s) other than Lp-PLA2 apparently being responsible for generating lysophosphatidylcholine.

show abstract

Section: Figure 6 Sb-222657 Prevents the Generation Of Oxidized Non-ementioning

confidence: 99%

Lipoprotein-associated phospholipase A2, platelet-activating factor acetylhydrolase, generates two bioactive products during the oxidation of low-density lipoprotein: use of a novel inhibitor

Macphee

Moores

Boyd

et al. 1999

Biochemical Journal

262

View full text Add to dashboard Cite

show abstract

“…However, there were no significant correlations between changes in LCAT activity and plasma cholesteryl esters or LCAT is a plasma enzyme of hepatic origin (1) that catalyses the transfer of an acyl group from lecithin to the 3-hydroxyl group of cholesterol, inducing the formation of cholesteryl ester (2). LCAT is a key enzyme in the metabolism of plasma lipoprotein phospholipids and cholesterol, and it may also indirectly influence the metabolism of triglycerides (3), because an increase in the free cholesterol content of LDL decreases the lipolysis of these particles (4). In addition, LCAT might play an important role in membrane integrity (2).…”

mentioning

confidence: 99%

Dietary Nucleotides Enhance Plasma Lecithin Cholesterol Acyl Transferase Activity and Apolipoprotein A-IV Concentration in Preterm Newborn Infants

et al. 1995

View full text Add to dashboard Cite

“…A decrease in plasma LCAT activity with a concomitant depletion of plasma CE was reported in African green monkeys to which lipopolysaccharides had been administered [1]. LCAT esterifies FC on the HDL surface [3,12]. We found that the CE concentration was decreased in the HDL and also in the very high-density lipoprotein (VHDL) fractions, not in the LDL and the VLDL fractions.…”

Section: Discussionmentioning

confidence: 51%

“…Room temperatures at 10 am were in the range of 24 to 29°C and humidities were 45 to 73% (experiments were done at June, 1997). A suspension of Lecithin:cholesterol acyltransferase (LCAT, EC 2.3.1.43) is the enzyme that catalyzes the transfer of fatty acids from phosphatidylcholine to free cholesterol (FC), and produces cholesteryl esters (CE) and lysophosphatidylcholine [3,12]. The enzyme is secreted by the liver and is associated with high-density lipoprotein (HDL).…”

Section: Bacterial and Viral Inoculationsmentioning

confidence: 99%

Reduced Serum Lecithin:Cholesterol Acyltransferase Activity and Cholesteryl Ester Concentration in Calves Experimentally Inoculated with Pasteurella haemolytica and Bovine Herpes Virus-1

Nakagawa¹,

Katoh

1999

The Journal of Veterinary Medical Science

View full text Add to dashboard Cite

ABSTRACT. Lecithin:cholesterol acyltransferase (LCAT), the enzyme responsible for esterification of cholesterol in plasma, is reported to be implicated in the regulation of inflammation in laboratory animals. The purpose of the present study was to elucidate the possible relevance of LCAT in the pathogenesis of calf pneumonia induced by inoculations of Pasteurella haemolytica and bovine herpes virus-1 into the calf lung. Serum LCAT activity was significantly (P<0.01) reduced in calves inoculated with Pasteurella haemolytica. The concentration of cholesteryl esters (CE), the product of the LCAT reaction, was also decreased in the inoculated group. Decreases in LCAT activity and the CE concentration were similarly observed in calves in which bovine herpes virus-1 was inoculated. In both bacteria-and virus-inoculated calves, CE concentrations in the high-density lipoprotein fractions were distinctly decreased, whereas those in the low-density lipoprotein fractions were practically unaltered. The acute-phase proteins haptoglobin and serum amyloid A were detected in sera from the bacteria-and virus-inoculated calves; however, the two acute-phase proteins were also found in sera from the control calves. These results suggest that decreases in LCAT activity and the CE concentration are involved in the pathogenesis of pneumonia induced by inoculation of calves with Pasteurella haemolytica and bovine herpes virus-1, and also that the change in the LCAT system is more intimately related to the occurrence of calf pneumonia than the induction of acute-phase proteins such as haptoglobin.-KEY WORDS: bovine, cholesteryl ester, high-density lipoprotein, lecithin:cholesterol acyltransferase, pneumonia.J. Vet. Med. Sci. 61(10): [1101][1102][1103][1104][1105][1106] 1999 enzyme is also reported to be responsible for hydrolyzing platelet-activating factor, the phospholipid (PL) having a broad range of biologic effects, including neutrophil activation and smooth muscle contraction [10]. An association of hypocholesterolemia with calf penumonia is observed in field cases (Nakagawa, unpublished results).The decreased cholesterol concentration in calves with pneumonia implies that LCAT activity is also reduced in those calves, because CE (in cattle serum, more than 80% of cholesterol is CE) is the product of the LCAT reaction. The purpose of the present study was to examine whether LCAT activity and the LCAT-related lipid concentrations are affected in experimental calf pneumonia. Pneumonia was induced by inoculation of calf lungs with Pasteurella haemolytica and bovine herpes virus-1 (BHV-1), the two major pathogens for calf pneumonia [5,7,19]. We report here that LCAT activity and the CE concentration are reduced in calves with pneumonia induced by both pathogens. MATERIALS AND METHODS Bacterial and viral inoculations:Twenty 2-to 3-monthold male Holstein calves weighing 72 to 108 kg were used to induce experimental pneumonic pasteurellosis [9,20]. Calves were housed individually in pens, and were acclimated for 2 weeks. Room temper...

show abstract

Lecithin: Cholesterol Acyltransferase and Intravascular Cholesterol Transport

Cited by 70 publications

References 182 publications

Lipoprotein-associated phospholipase A2, platelet-activating factor acetylhydrolase, generates two bioactive products during the oxidation of low-density lipoprotein: use of a novel inhibitor

Lipoprotein-associated phospholipase A2, platelet-activating factor acetylhydrolase, generates two bioactive products during the oxidation of low-density lipoprotein: use of a novel inhibitor

Dietary Nucleotides Enhance Plasma Lecithin Cholesterol Acyl Transferase Activity and Apolipoprotein A-IV Concentration in Preterm Newborn Infants

Reduced Serum Lecithin:Cholesterol Acyltransferase Activity and Cholesteryl Ester Concentration in Calves Experimentally Inoculated with Pasteurella haemolytica and Bovine Herpes Virus-1

Contact Info

Product

Resources

About