Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Methods for quantitation of the major apoproteins of human serum very low density lipoprotein have been developed employing tetramethylurea, which delipidates the lipoprotein and selectively precipitates apolipoprotein B. Six soluble apoproteins are separated by electrophoresis in polyacrylamide gel. One of these is a previously unrecognized species of R-alanine (R4-alanine), more anionic than the R3-alanine polypeptide. Conditions of staining have been found which yield reproducibly linear chromogenic response with native lipoprotein and with each purified apoprotein. Recovery of protein in the seven species measured accounts for over 97% of the total in the very low density lipoprotein of normolipidemic individuals and in most samples from individuals with endogenous hyperlipemia. The mean content of apolipoprotein B in 43 samples from normolipidemic subjects was 36.9(+/-1.2 SEM)% of total protein, The distribution of the major soluble apoproteins as mean (+/-SEM) percentage of the soluble fraction was : R-serine, 5.3+/-o.5; arginine-rich, 20.6+/-1.0; R-glutamic, 10.6+/-0.4; R2-alanine, 28.3+/-0.7; R3-alanine, 26.9+/-0.5; and R4-alanine, 8.0+/-0.5. Distribution of the apoproteins was a function of particle diameter of very low density lipoprotein in fractions separated by gel permeation chromatography and by density gradient ultracentrifugation. In fractions below 700-800 A, apolipoprotein B comprised an increasing percentage of the total protein with decreasing particle diameter. Among the soluble proteins the percentage of the arginine-rich and R-serine polypeptides increased and that of the R-glutamic polypeptide declined progressively with decreasing particle size. Apoprotein distribution was similar in fractions of similar particle size from normolipidemic and hyperlipemic subjects with the exception that all fractions from the hyperlipemic subjects contained more R-serine and some, more arginine rich polypeptide. Even in the absence of chylomicrons, the distribution of soluble apoproteins in particles of diameters greater than 700-800 A was usually similar to that of the smallest particles. This suggests that the largest particles may include products of the partial catabolism of chylomicrons.
 ...
PMID:Apoprotein composition of very low density lipoproteins of human serum. 17 34

The prevalence of ischemic heart disease is significantly lower in southwestern American Indians than in Caucasians. To investigate this difference, the metabolism of low density lipoprotein apoprotein (apo-LDL) and plasma lipoprotein cholesterol composition were studied in 10 southwestern American Indians and 5 Caucasian controls. The plasma concentration of LDL cholesterol in American Indians was 88 +/- 5 mg/dl (mean +/- SEM) and 111 +/- 7 mg/dl in Caucasians. The corresponding values of apo-LDL concentrations were 53 +/- 3 mg/dl and 77 +/- 4 mg/dl, respectively. Conversely, high density lipoprotein cholesterol (HDL) concentrations were significantly higher in American Indians (56 +/- 4 mg/dl) than in Caucasians (37 +/- 3 mg/dl). There were no statistically significant differences in the biological half-life of apo-LDL, calculated from the second exponential of the plasma die-away curve (3.06 +/- 0.15 days vs. 3.45 +/- 0.11 days), the fractional catabolic rate of apo-LDL (0.432 +/- 0.01 vs. 0.411 +/- 0.01), or the fraction of total exchangeable apo-LDL in the intravascular space (70 +/- 1 vs. 67 +/- 3%). As derived from the absolute catabolic rate under steady-state conditions, the synthetic rate of apo-LDL in American Indians was, however, significantly lower than in Caucasians (334.6 +/- 7.8 mg/m(2) per day vs. 507.2 +/- 6.7 mg/m(2) per day; P < 0.001). These data indicate that the lower levels of plasma LDL cholesterol and apo-LDL in American Indians are due to a reduced rate of apo-LDL synthesis rather than to differences in fractional catabolic rates. These differences, in combination with higher HDL cholesterol levels, may contribute to the lower prevalence of ischemic heart disease in American Indians.
 ...
PMID:Low density lipoprotein metabolism and lipoprotein cholesterol content in southwestern American Indians. 22 Mar 52

A radioimmunoassay for the binding protein for vitamin D and its metabolites (DBP) has been developed. Suitable rabbit anti-DBP antiserum was elicited after primary and one booster injection. Anti-DBP antisera, as well as antigroup-specific component antisera, produced a single, monospecific line of percipitation when reacted against purified DBP and human serum. DBP was iodinated with 125I and 125I-DBP was purified by gel filtration on Sephadex G-200. Binding of 125I-DBP by 20 nl of rabbit anti-DBP antisera was approximately 50% and was sharply competed for by 0.4-4.0 ng of DBP standard. Displacement of 125I-DBP by human serum dilutions or standard DBP gave identical curves, and only weak competition was observed with old and new world primate sera. Apo- and holo-DBP possessed indistinguishable immunoreactivity. The assay detects DBP in 1-10 nl of human serum with reasonable accuracy and with reasonable intra- and interassay precision. The mean serum concentration (+/- SEM) for a group of 40 normal adults was 525 +/- 24 mug/ml and no sex difference was observed. Higher levels were found in sera from pregnant women and women receiving oral contraceptives, and decreased concentrations were observed in premature cord and hypoproteinemic sera. No significant correlation between serum DBP levels and serum 25-hydroxycalciferol levels was found, and the DBP content of sera from vitamin D-deprived and vitamin D-treated subjects was indistinguishable from that of normal adults. DBP accounts for 6- of the alpha globulin in normal human serum. Considering the normal serum content of the parent vitamin and its metabolites to be approximately 0.1-0.2 mum, these immunoassay data confirm previous saturation analyses of human serum antiricketic sterol-binding capacity and suggest that greater than 95% of DBP circulates as the apoprotein under normal conditions.
 ...
PMID:Radioimmunoassay of the binding protein for vitamin D and its metabolites in human serum: concentrations in normal subjects and patients with disorders of mineral homeostasis. 108 57

In the present study, the accumulation of apolipoproteins (apo) A-I, B, and E in culture medium was measured after 0, 3, 6, 12, and 24 h of incubation with 150 microM docosahexaenoic acid complexed to 75 microM bovine serum albumin (BSA-22:6), either in the presence or absence of 50 micrograms/ml cholesterol and 4 micrograms/ml 25-hydroxycholesterol (C/25-OH). HepG2 cells incubated with BSA + C/25-OH for 24 h accumulated approximately 2.0-fold greater apoE and B as compared to BSA-treated cells. Moreover, HepG2 cell apoB accumulation after 24 h of BSA-22:6 treatment was approximately 2.0-fold greater than apoB accumulation from cells treated with BSA alone. When BSA-22:6 and C/25-OH were both included in the incubation, apoB accumulation was approximately 5.0-fold greater than BSA-treated cells. Comparative studies using BSA-18:1 were carried out for 24 h and showed similar levels of apoA-I, B, and E accumulation in culture medium as compared to BSA-22:6-treated cells. In addition, apoA-I, B, and E mRNA abundance were found to be unaffected by type of fatty acid treatment or length of incubation, averaging 48.2 +/- 7.5, 222 +/- 33.6, and 17.1 +/- 0.7 pg mRNA/micrograms RNA (mean +/- SEM), respectively. As the accumulation of apoB and apoE in culture medium may be modified by HepG2 cell LDL receptor expression, LDL receptor mRNA abundance and LDL receptor activity were quantified at various times over the course of the study. By 6 h of BSA + C/25-OH treatment, LDL receptor mRNA was reduced approximately 2.3-fold, while receptor activity was reduced approximately 1.5-fold, as compared to BSA controls. In an experiment designed to determine uptake of HepG2 cell lipoproteins, 3H-labeled apoB-containing lipoproteins derived from HepG2 cells were prepared. The 3H-labeled lipoproteins were 1.25-fold more likely to be removed from the media of HepG2 cells treated with BSA than from cells treated with BSA + C/25-OH. From these results, we postulate that HepG2 cell LDL receptor activity mediates the removal of apoB, E-containing lipoproteins from culture medium and contributes to the lower accumulation of apoB and E observed in culture medium from cells treated with BSA as compared to cells treated with C/25-OH.
 ...
PMID:HepG2 cell LDL receptor activity and the accumulation of apolipoprotein B and E in response to docosahexaenoic acid and cholesterol. 143 95

The effect of exclusive lactation on lipid levels was investigated by evaluating serum concentrations of total and lipoprotein cholesterol, triglyceride (TG), and apoprotein (apo) B in mothers during and after exclusive, prolonged lactation. Serum total cholesterol concentrations were measured at delivery (n = 195), at 2 (n = 165), 6 (n = 119), 9 (n = 74), and 12 months (n = 32) of lactation, and 2 months (n = 27) after ending this exclusive lactation. In a subgroup of 34 mothers, serum levels of very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL), high-density lipoprotein 2 (HDL2), HDL3, and LDL apo B were determined at 2, 6, 9, and 12 months of lactation. The mean value of serum total cholesterol concentrations decreased from 6.2 +/- 0.12 (SEM; n = 195) at delivery to 4.8 +/- 0.1 mmol/L (n = 116) at 6 months of exclusive lactation (P < .001). The average decrement in total cholesterol level was 0.80 mmol/L (P < .001) from delivery to 2 months of lactation and 0.55 mmol/L (P < .001) from 2 to 6 months of lactation, and levels were stable thereafter. In the 27 mothers who were exclusively breast-feeding their infants at 9 months of lactation and whose serum cholesterol levels were measured 2 months after the end of lactation, cholesterol levels increased rapidly to 5.7 +/- 0.21 mmol/L (P = .001). In the subgroup of 34 mothers who were examined more closely, the course just described was also true for serum TG, LDL and VLDL cholesterol, and LDL apo B levels.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Serum cholesterol and lipoprotein concentrations in mothers during and after prolonged exclusive lactation. 146 Nov 38

Lipid and apoprotein composition of four very low density lipoprotein (VLDL) subfractions decreasing in Sf value were evaluated in the fasting state in 12 normolipidemic Pima Indians (6 M, 6 F, age 39 +/- 1.7 yrs) (mean +/- SEM) with non-insulin-dependent diabetes mellitus (NIDDM) in poor glycemic control (HbA1 9.8 +/- 2.9%) and in 14 normoglycemic Pima controls matched for age, BMI and lipid values. Total cholesterol (CHOL), triglyceride (TG), phospholipids (PL), total protein (TP), apo B, apo CII, apo CIII and apoE were assayed in total VLDL and in each of the four VLDL subfractions designed as A (Sf greater than 400), B (Sf 175-400), C (Sf 100-175), and D (Sf 20-100). Diabetics compared to nondiabetics had higher concentrations of all constituents of VLDL D, with the largest changes being in TG (38.0 +/- 3.8 vs 28.0 +/- 2.5 mg/dl, P less than 0.04), PL (14.0 +/- 1.3 vs 10.0 +/- 1.0 mg/dl, P less than 0.04), TP (9.8 +/- 0.8 vs 7.6 +/- 2.4 mg/dl, P less than 0.05), apo B (6.3 +/- 0.5 vs 4.7 +/- 0.4 mg/dl, P less than 0.03) and apoE (0.73 +/- 0.09 vs 0.52 +/- 0.04 mg/dl, P less than 0.04). Since no difference was found between the groups in percentage composition of lipids or apoproteins in total VLDL and in all VLDL subfractions, the data suggest that in diabetics, even when normolipidemic, there is an increase in the number rather than in the composition of the smallest VLDL subfraction (VLDL D), which are usually considered to be more atherogenic.
 ...
PMID:Alterations in very low density lipoprotein subfractions in normotriglyceridemic non-insulin-dependent diabetics. 181 50

A cDNA clone containing the coding region for cynomolgus monkey cholesteryl ester transfer protein (CETP) was isolated by the polymerase chain reaction with primers based on the human CETP cDNA sequence and cDNA synthesized from liver poly (A+) RNA. Analysis of that cDNA indicated that the nucleotide and amino acid sequences of cynomolgus monkey CETP were greater than 95% homologous with the human sequences. A fragment of the cDNA was used to develop an internal-standard/RNAse protection assay that allowed precise quantification of CETP mRNA levels. Analysis of total RNA from various tissues with this assay revealed that the liver and thoracic aorta expressed high levels of CETP mRNA; the mesenteric fat, adrenal gland, spleen, and abdominal aorta had low but detectable levels of the mRNA; and the brain, kidney, intestine, and skeletal muscle had undetectable levels of that mRNA. When the monkeys were made hypercholesterolemic by a high-fat, high-cholesterol (HFHC) diet, hepatic levels of CETP mRNA increased from 1.6 +/- 0.4 pg/micrograms total RNA (mean +/- SEM) to 4.1 +/- 0.8 pg/micrograms (p less than 0.005); mesenteric fat CETP mRNA increased from 0.4 +/- 0.1 pg/micrograms total RNA to 5.3 +/- 2.2 pg/micrograms (p less than 0.05); and plasma CET activity increased approximately fourfold. The CETP mRNA levels in the thoracic and abdominal aortas were not significantly increased in monkeys fed the HFHC diet, even though those animals had gross atherosclerosis. The apoprotein E mRNA levels, however, were markedly increased in the aortas of monkeys with atherosclerosis, with the largest increase occurring in the abdominal aorta. Taken together, these data suggest that lipid deposition in the artery was not accompanied by increased expression of the CETP gene in that tissue. Statistical analysis showed that a strong, negative correlation existed between hepatic CETP mRNA levels and both high density lipoprotein cholesterol (r = -0.85, p less than 0.001) and apoprotein A-I (r = -0.84, p less than 0.001). These data suggest that HFHC diet-induced changes in high density lipoprotein metabolism may be linked to altered expression of a function CETP gene.
 ...
PMID:Molecular cloning, sequence, and expression of cynomolgus monkey cholesteryl ester transfer protein. Inverse correlation between hepatic cholesteryl ester transfer protein mRNA levels and plasma high density lipoprotein levels. 193 78

The effect of prazosin treatment on blood pressure, plasma HDL-cholesterol concentration, and apoprotein-AI/HDL (apoAI/HDL) kinetics was studied in 11 patients with mild hypertension. Blood pressure (mean +/- SEM) fell from 143 +/- 1/96 +/- 1 to 134 +/- 1/86 +/- 1 mm Hg after 4 to 5 months of prazosin treatment (P less than .001), associated with an increase in plasma HDL-cholesterol concentration from 38 +/- 2 to 46 +/- 2 mg/dL (P less than .001). Both the fractional catabolic rate (FCR) and total synthetic rate of apoAI/HDL, which were higher than previous reported values for normal individuals, decreased from 0.36 +/- 0.02 to 0.30 +/- 0.02 L/day and 17.4 +/- 1.1 to 13.8 +/- 1.1 mg/kg/min, respectively. These changes were statistically significant, and the post-treatment values for both variables were now within the normal range. When the decay curve was further analyzed by nonlinear curve fitting, it was shown that the return to normal of the FCR of apoAI/HDL in patients treated with prazosin was accounted for by the decrease of the decay constants of the second [p(2)] and third [p(3)] components of the 125I-AI/HDL disappearance curve. In conclusion, abnormalities in HDL concentration and HDL kinetics exist in patients with very mild hypertension. These defects were significantly improved with prazosin treatment, and this may render the compound of particular clinical benefit in the treatment of patients with mild hypertension.
 ...
PMID:Effect of prazosin treatment on HDL kinetics in patients with hypertension. 212 Nov 64

To study the role of the two postheparin plasma lipolytic enzymes, lipoprotein lipase (LPL) and hepatic lipase (HL) in high density lipoprotein (HDL) metabolism at a population level, we determined serum lipoproteins, apoproteins A-I, A-II, B, and E, and postheparin plasma LPL and HL activities in 65 subjects with a mean HDL-cholesterol of 34 mg/dl and in 62 subjects with a mean HDL-cholesterol of 87 mg/dl. These two groups represented the highest and lowest 1.4 percentile of a random sample consisting 4,970 subjects. The variation in HDL level was due to a 4.1-fold difference in the HDL2 cholesterol (P less than 0.001) whereas the HDL3 cholesterol level was increased only by 32% (P less than 0.001) in the group with high HDL-cholesterol. Serum apoA-levels were 128 +/- 2.2 mg/dl and 210 +/- 2.8 mg/dl (mean +/- SEM) in hypo- and hyper-HDL cholesterolemia, respectively. Serum apoA-II concentration was elevated by 28% (P less than 0.001) in hyperalphalipoproteinemia. The apoA-I/A-II ratio was elevated only in women with high HDL-cholesterol but not in men, suggesting that elevation of apoA-I is involved in hyperalphalipoproteinemia in females, whereas both apoA proteins are elevated in men with high HDL cholesterol. Serum concentration of apoE and its phenotype distribution were similar in the two groups. The HL activity was reduced in the high HDL-cholesterol group (21.2 +/- 1.5 vs. 38.5 +/- 1.8 mumol/h/ml, P less than 0.001), whereas the LPL activity was elevated in the group with high HDL-cholesterol compared to subjects with low HDL-cholesterol (27.8 +/- 1.3 vs. 19.9 +/- 0.8 mumol/h/ml, P less than 0.001). The HL and LPL activities correlated in opposing ways with the HDL2 cholesterol (r = 0.57, P less than 0.001 and r = 0.51, P less than 0.001, respectively), and this appeared to be independent of the relative ponderosity by multiple correlation analysis. The results demonstrate major influence of both HL and LPL on serum HDL cholesterol concentration at a population level.
 ...
PMID:Postheparin plasma lipoprotein and hepatic lipase are determinants of hypo- and hyperalphalipoproteinemia. 250 59

Very-low-density lipoproteins (VLDL) (density less than 1.006 g/mL) were isolated from type I (insulin-dependent) diabetic patients in good to fair glycemic control and from age-, sex-, and race-matched, nondiabetic, control subjects. VLDL were incubated with human, monocyte-derived macrophages obtained from nondiabetic donors, and the rates of cellular cholesteryl ester synthesis and cholesterol accumulation were determined. VLDL isolated from diabetic patients stimulated significantly more cholesteryl ester synthesis than did VLDL isolated from control subjects (4.04 +/- 1.01 v 1.99 +/- 0.39 nmol 14C-cholesteryl oleate synthesized/mg cell protein/20 h; mean +/- SEM, P less than .05). The stimulation of cholesteryl ester synthesis in macrophages incubated with VLDL isolated from diabetic patients was paralleled by a significant increase in intracellular cholesteryl ester accumulation (P less than .05). The increase in cholesteryl ester synthesis and accumulation in macrophages were mediated by a significant increase in the receptor mediated, high affinity degradation (2.55 +/- 0.23 v 2.12 +/- 0.20 micrograms degraded/mg cell protein/20 h) and accumulation (283 +/- 35 v 242 +/- 33 ng/mg cell protein/20 h) of 125I-VLDL isolated from diabetic patients compared with VLDL from control subjects. To determine if changes in VLDL apoprotein composition were responsible for the observed changes in cellular rates of cholesteryl ester synthesis and accumulation, we also examined the apoprotein composition of the VLDL from both groups. There were no significant differences between the apoproteins B, E, and C content of VLDL from both groups. We also determined the chemical composition of VLDL isolated from both groups of subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Interaction of very-low-density lipoprotein isolated from type I (insulin-dependent) diabetic subjects with human monocyte-derived macrophages. 255 94


1 2 3 4 5 Next >>