Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied 56 patients affected by primary hypercholesterolemia treated with placebo for 1 month and with simvastatin (20 mg/day) or pravastatin (20 mg/day) for 6 months during a double-blind clinical trial. At 1-month intervals we determined the following parameters in the serum: total and HDL cholesterol, triglycerides, and apolipoprotein A-1 and B. At the same time intervals we also determined the cholesterol and phospholipid concentration, the Na+/K+ ATPase activity, and the fluidity of erythrocyte membranes. Our results demonstrated the following modifications in the erythrocyte membranes during simvastatin and pravastatin treatments: (1) an initial increase in cholesterol concentration and in cholesterol/phospholipid molar ratio, with a significant decrease only after 4 months; (2) a similar behavior of membrane fluidity, with an initial decrease and an elevation after 4 months; (3) an increase in the Na+/K+ ATPase activity only after 4 months. We hypothesize that simvastatin and pravastatin not only inhibit the hepatic synthesis of cholesterol, but also modify the cholesterol exchange between plasma and the erythrocyte membrane.
Exp Mol Pathol 1993 Aug
PMID:Effect of hydroxymethylglutaryl-CoA reductase inhibitors on the functional properties of erythrocyte membranes. 826 65

In order to investigate the effects of two contraceptive steroids given orally, which contain ethinyl estradiol in combination with different types and doses of progestins, on plasma lipoprotein metabolism, rat groups named according to progestin components were designated as short-and long-term groups of norethisterone acetate and levonorgestrel at low-and high-doses. At the end of the experiments, plasma triglyceride, phospholipid, apolipoprotein A1 and B, LDL-, HDL-, HDL2- and HDL3-cholesterol levels and hepatic lipase activity were measured. When compared to controls, phospholipid and LDL-cholesterol were increased in all groups; triglyceride levels were also increased in all short-term groups, but only in low-dose norethisterone and high-dose levonorgestrel of long-term groups. HDL- and HDL3- cholesterol were decreased in all groups, except in low-dose levonorgestrel groups, but HDL2-cholesterol were lower only at high doses and long period. In short-term, an increase in apolipoprotein A1 levels was significantly important at high doses; in long-term apolipoprotein A1 was increased at low doses, while decreased at high doses. Apolipoprotein B was elevated only in long-term high dose of norethisterone acetate group. Hepatic lipase activity was increased in long-term high-dose of levonorgestrel group, whereas decreased in all other groups. In conclusion, the data presented was interpreted that the effects of these combinations used in the study on plasma lipoprotein metabolism may be related to the changes observed in hepatic lipase activity.
Biochem Mol Biol Int 1993 Jun
PMID:The effect of contraceptive steroids on plasma lipoprotein metabolism in female rats (II). 836 6

Trypanosoma brucei S427cl1 organisms made 6 divisions in modified minimal essential medium (BMEM) supplemented with fetal bovine serum (FBS)-low or high density lipoprotein (LDL, HDL) and fatty acid-free bovine serum albumin (FAF-BSA). Omission of lipoproteins or FAF-BSA from the medium caused the parasites to accumulate in G1 of the cell cycle and to lose the ability to replicate at 37 degrees C. Proteinase K-treated LDL or HDL, which did not have detectable apolipoprotein, supported the G1 to S cell cycle transition of T. brucei S427cl1 organisms in BMEM supplemented with FAF-BSA. Addition of C6:0, C7:0 or fatty C8:0 fatty acid (1 mol fatty acid mol-1 FAF-BSA in the incubation mixture) to serum-free medium supplemented with LDL or HDL and FAF-BSA prevented T. brucei S427cl1 organisms from progressing through G1 into S of the cell cycle. T. brucei S427cl1 organisms became stumpy-like forms during plateau phase growth under axenic conditions. Stumpy-like T. brucei S427cl1 organisms were mainly in G1 of the cell cycle, expressed raised levels of NAD diaphorase activity, were unable to replicate at 37 degrees C, but were able to differentiate to replicating procyclic organisms. Medium collected from plateau phase cultures of T. brucei S427cl1 did not support the G1 to S cell cycle transition of exponentially growing T. brucei organisms. The capacity of plateau phase medium to support G1 to S transition of T. brucei S427cl1 organisms was restored by addition of FAF-BSA and its capacity to support 4 cycles of replication of the parasites was restored by addition of FAF-BSA and LDL or HDL.
Mol Biochem Parasitol 1993 Feb
PMID:Control of G1 to S cell cycle progression of Trypanosoma brucei S427cl1 organisms under axenic conditions. 843 15

Considerable variability exists among individuals in the response of plasma cholesterol to changes in dietary fat and cholesterol, and obesity is one variable reported to affect this response. This study was performed to determine the relationship between body fat and changes in plasma cholesterol in cynomolgus monkeys fed a high-fat cholesterol-containing diet for 12 months. The animals gained significant body weight (body mass index increased from 30.5 +/- 0.5 to 35.7 +/- 2.8 kg/m2) and skinfold parameters of body fat increased as well. Total cholesterol increased from 109 +/- 4 to 390 +/- 25 mg/dl (P < 0.001), and there were also significant increases in LDL- and HDL-cholesterol and triglyceride. While there was very little relationship between body fat and plasma lipids before the diet, after 12 months, there were significant negative correlations between total and LDL-cholesterol and anthropometric measures of body fat (r ranged from -0.37 to -0.55, P < 0.01). The correlations were not affected when the effects of baseline body mass index and serum cholesterol and total food intake were controlled by partial correlation analysis. In this sample of animals, the acquisition of greater body fat appeared to protect against rises in cholesterol in response to consumption of a high-fat cholesterol-containing diet.
Exp Mol Pathol 1993 Feb
PMID:Body fat and fat distribution by anthropometry and the response to high-fat cholesterol-containing diet in monkeys. 845 36

Feeding a diet enriched with cholesterol/cholic acid (CCA) to rats caused defective plasma clearance of labeled chylomicron-like emulsions compared with clearance in chow-fed rats. When heparin was injected 5 min before an emulsion, the clearance of the emulsion in CCA-fed rats was significantly improved, and lipoproteins in the remnant and HDL fractions of plasma became enriched in apolipoprotein E. Injection of lactoferrin or poly-arginine inhibited the removal of emulsion or lymph chylomicron cholesteryl oleate in regular chow-fed rats. Poly-arginine but not lactoferrin inhibited the clearance of emulsion or chylomicron triolein also. The results demonstrate the involvement of charge interactions in both the lipolysis and remnant uptake steps of chylomicron clearance.
Biochem Mol Biol Int 1993 Apr
PMID:Charge effects on chylomicron clearance in rats. 850 43

We performed denaturing gradient gel electrophoresis (DGGE) of exons 4, 5, 6 and their exon-intron boundaries of the LPL-gene in 169 unrelated male patients suffering from familial combined hyperlipidemia (FCH). Twenty patients were found to carry a nucleotide substitution in exon 6. Sequence and PCR/digestion analysis revealed one common mutation (Asn291Ser) in all these cases. This mutation was talso present in 215 male controls, albeit at a lower frequency than in FCH patients (10/215 = 4.6% vs. 20/169 = 11.8%; p < 0.02). Analysis of lipid, lipoprotein and apolipoprotein levels demonstrated an association between the presence of this Asn291Ser substitution and decreased HDL-cholesterol (0.94 +/- 0.31 vs. 1.12 +/- 0.26 mmol/l; p < 0.04) in our controls. FCH patients carrying this mutation showed decreased HDL-cholesterol (0.75 +/- 0.16 vs. 0.95 +/- 0.36 mmol/l; p = 0.05) and increased triglyceride levels (5.96 +/- 4.12 vs. 3.48 +/- 1.78 mmol/l; p < 0.005) compared to non-carriers. The high triglyceride and low HDL-cholesterol phenotype in carriers of this substitution was most obvious when BMI exceeded 27 kg/m2. Our study of male FCH patients revealed the presence of a common mutation in the LPL-gene that is associated with lipoprotein abnormalities, indicating that defective LPL is at least one of the factors contributing to the FCH-phenotype.
Hum Mol Genet 1995 Sep
PMID:A frequently occurring mutation in the lipoprotein lipase gene (Asn291Ser) contributes to the expression of familial combined hyperlipidemia. 854 37

The study addressed to understand whether or not lipoproteins at low concentrations could modulate Receptor-'C' dependent platelet signalling revealed that LDL, like exogenous cholesterol, had the capacity to initiate PLD-dependent platelet signalling in a dose dependent fashion and this effect was inhibited in presence of HDL; cAMP; DTT; Zn++ and butanol whereas cGMP had no effect upon this PLD-dependent signalling. Further Receptor 'C' from platelet in the purified-form displayed LDL-or cholesterol-dependent autophosphorylation at the tyrosine residues and this Receptor-'C' tyrosine kinase (Receptor-Ck) activity contributed to the observed LDL-or cholesterol -dependent PLD activity in human platelets. Based upon these results coupled with earlier results, an attempt was made to define the lipoprotein-dependent platelet signalling pathway.
Mol Cell Biochem 1995 Oct 18
PMID:Lipoprotein receptor 'CK'--dependent signalling in human platelets. 856 63

Platelet aggregation sensitivity was assessed in nine species of animals, including humans, with disparate susceptibility to atherosclerosis and a wide range in their LDL/HDL profiles. Platelet aggregation sensitivity between species varied almost 20-fold. The most sensitive platelets were found in humans and rabbits, followed by squirrel and rhesus monkeys with the most resistant platelets in cats, hamsters, rats, cebus monkeys, and gerbils. Species platelet aggregation sensitivity correlated well with relative susceptibility to atherosclerosis. The relationship between LDL/HDL ratio and platelet aggregation was significant, both across species (r = 0.76, without cebus) and within species (r = 0.50 for humans).
Comp Biochem Physiol B Biochem Mol Biol 1996 Feb
PMID:Sensitivity to platelet aggregation appears related to the lipoprotein profile and atherosclerosis risk in humans and across species. 865 88

The aim of the present investigation was to study the regulation of apolipoprotein E by two dietary nutrients, saturated fat and cholesterol, known to raise plasma cholesterol levels. ApoE is a protein component of several classes of lipoproteins including VLDL and HDL, and dietary lipids may regulate VLDL and apoE-containing HDL particles through their effects on apoE gene. Male rats and mice were fed the following 4 diets: control diet (C); high cholesterol diet with 0.5% cholesterol (HC); high fat diet with 20% hydrogenated coconut oil (HF); and high fat plus high cholesterol diet with 0.5% cholesterol and 20% fat (HF/ C). Plasma cholesterol levels remained unchanged on HC diet, but in mice VLDL-cholesterol increased by 31%. HF diet increased VLDL and LDL by 15-17% in rats, and 21% in mice. A combination of fat and cholesterol diet showed pronounced effects on plasma lipoprotein concentrations, raising apoB-containing particles by 21% and 44% in mice and rats, respectively. Plasma apoE levels increased significantly on all diets. The mechanism of regulation of increased plasma apoB and apoE levels was examined. Quantification of hepatic apoB mRNA showed a lack of correlation between plasma apoB and hepatic apoB mRNA levels, suggesting that posttranscriptional regulation increased plasma apoB-containing lipoproteins in animals fed saturated fat diets. Hepatic apoE mRNA levels increased significantly in animals fed cholesterol-rich diets. However, despite increased plasma apoE levels on diet containing only saturated fat, hepatic apoE mRNA did not change. Synthesis of apoE on the liver polysomes increased selectively on cholesterol-rich diets. These results suggest that cholesterol-rich diets altered apoE, in part, by transcriptional mechanism, and saturated fat-rich diets increased plasma apoE levels by posttranscriptional mechanism, possibly decreased receptor-mediated uptake of apoE-containing particles. The regulation of LDL receptor was also studied since plasma apoB and E levels may be altered by LDL receptor-mediated uptake by the hepatocytes. As expected, high cholesterol diet decreased LDL receptor mRNA by 30-40%. However, the LDL receptor protein on liver membranes did not change on any of the test diets in both animal species. Hepatic cholesterol content increased several fold selectively on high cholesterol diets. These findings suggest that: 1) both transcriptional and posttranscriptional mechanisms are important in regulating plasma apoB and E containing lipoproteins; 2) dietary cholesterol regulates apoE gene by a transcriptional mechanism and dietary saturated fat by posttranscriptional mechanism; and 3) changes in the hepatic apoE and LDL receptor mRNA are associated with the changes in intracellular cholesterol concentrations.
Mol Cell Biochem 1996 Feb 23
PMID:Regulation of the apolipoprotein E by dietary lipids occurs by transcriptional and post-transcriptional mechanisms. 870 Jan 60

Site-directed mutagenesis of the acute-phase human serum amyloid A (SAA1 alpha) protein was used to evaluate the importance of the N-terminal amino acid residues, namely RSFFSFLGEAF The full-length cDNA clone of SAA1 alpha (pA1.mod.) was used to create two mutations, namely Gly-8 to Asp-8 and an 11 amino acid truncation between Arg-1 and Phe-11 respectively. Wild-type and mutant cDNAs were expressed in Chinese hamster ovary (CHO) cells under the control of the human cytomegalovirus promoter, which resulted in the secretion of the processed proteins into the culture media. Wild-type recombinant human SAA (rSAA) protein was shown to have pI values of 6.0 and 6.4, similar to the human SAA isoform SAA1 alpha and SAA1 alpha desArg found in acute-phase plasma. N-terminal sequencing of 56 residues confirmed its identity with human SAA1 alpha. The total yield of wild-type rSAA measured by ELISA was between 3.5 and 30 mg/l. The two mutations resulted in reduced expression levels of the mutant SAA proteins (3-10 mg/l). Further measurements of rSAA concentration in lipid fractions of culture medium collected at a density of 1.21 g/ml (high-density liporotein; HDL) and 1.063-1.18 g/ml (very-low-density lipoprotein/low-density lipoprotein; VLDL/LDL) showed that 76% of the wild-type protein was found in the HDL fraction and the remaining 24% in the infranatant non-lipid fraction. In contrast the relative concentration of mutant rSAA in HDL and infranatant fractions was reversed. This is consistent with the previously proposed involvement of the 11 amino acid peptide in anchoring. SAA protein on to HDL3 [Turnell, Sarra, Glover, Baum, Caspi, Baltz and Pepys (1986) Mol. Biol. Med. 3, 387-407]. Wild-type rSAA protein was shown to from amyloid fibrils in vitro under acidic conditions as shown by electron microscopy, and stained positive with Congo Red and exhibited apple-green birefringence when viewed under polarized light. Under the same conditions mutSAA(G8D) and mutSAA delta 1-11 did not form amyloid fibrils. In conclusion, replacement of Gly-8 by Asp-8 or deletion of the first 11 amino acid residues at the N-terminus of rSAA diminishes its capacity to bind to HDL and decreases amyloid fibril formation.
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PMID:Expression of recombinant human serum amyloid A in mammalian cells and demonstration of the region necessary for high-density lipoprotein binding and amyloid fibril formation by site-directed mutagenesis. 883 54


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