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Biomedical subjects

E L Bierman

Publications and source records attributed to E L Bierman.

At least 91 records · Page 5Linked to original sources
PubMed1980

Triacylglycerol metabolism and triacylglycerol lipase activities of cultured human skin fibroblasts.

The relative contribution of lipoproteins and free fatty acid to the cellular triacylglycerol content of cultured human fibroblasts was tested. Fibroblasts accumulated triacylglycerol in proportion to the molar ratio of free fatty acid (oleic acid) to albumin in the medium. Fibroblasts also accumulated triacylglycerol when exposed to medium containing human very low density liproprotein. This accumulation of triacylglycerol was apparently due to direct uptake of intact very low density lipoprotein particles initiated by binding of very low density lipoprotein to cell surface receptors. The amount of 125I-labeled very low density lipoprotein protein internalized and degraded by the cell saturated at the same very low density lipoprotein concentration that produced the maximum increase in cell triacylglycerol. Preincubations with lipoprotein-deficient serum, which enhanced the cell's ability to bind 125I-labeled very low density lipoprotein, increased the amount of 125I-labeled very low density lipoprotein internalized and degraded by the cell in parallel with increased levels of cellular triacylglycerol. Results suggest that the triacylglycerol that accumulates in the presence of very low density lipoprotein represents a lysosomal pool of partially degraded very low density lipoprotein. Measurements of lipase activity of fibroblast homogenates revealed three pH optima at (in descending order of magnitude of activity) pH 4, pH 6, and pH 8. The pH 8 lipase does not appear to represent lipoprotein lipase, since it is not activated by either serum or heparin. Exposure of the cells to medium with varying lipid composition had no effect on the lipase activities. The lipase activities of fibroblasts from donors with familial hypertriglyceridemia appear to be normal.

Adult↗
PubMed1980

Sphingomyelin suppresses the binding and utilization of low density lipoproteins by skin fibroblasts.

Cultured human skin fibroblasts incubated at 37 degrees C with sonically dispersed, positively charged liposomes containing sphingomyelin internalized and metabolized the phospholipid. Sphingomyelin incorporation into the cells produced a reduction in low density lipoprotein binding and degradation. Lecithin-containing liposomes were much less effective. In addition, incubation with sphingomyelin resulted in a marked increase in acetate incorporation into sterol. These results suggest that sphingomyelin, which is required by cells for membrane synthesis, can influence the regulation of the cell surface low density lipoprotein receptor and intracellular cholesterol balance.

Cells, Cultured↗
PubMed1980

Rapid regulation of the activity of the low density lipoprotein receptor of cultured human fibroblasts.

Regulation of low density lipoprotein (LDL) receptor activity of cultured human skin fibroblasts was studied by measuring 4 degrees C binding of 125I-LDL after cells were incubated at 37 degrees C with medium containing varying lipoprotein and serum compositions. When cells grown on medium containing 10% human whole serum were exposed to medium containing 10% human lipoprotein-deficient serum, LDL receptor activity increased within 4 h and then decreased between 12 and 24 h. This early, transient increase in binding was inhibited by cycloheximide, suggesting that new protein synthesis was involved. Changing the medium also produced a drop in cell total cholesterol content within the first 4 h, suggesting that cholesterol efflux initiated the rapid increase in LDL receptor activity. Cells incubated for 4 h with medium designed to promote cholesterol flux into the cell (plus whole serum or LDL) or minimize efflux (no serum or lipoprotein-"free" medium) had lower LDL receptor activities than cells incubated for 4 h with medium that appeared to promote cholesterol efflux (plus lipoprotein-deficient serum or high density lipoproteins3). The promotion of cholesterol efflux and acute activation of the LDL receptor by lipoprotein-deficient serum appear to be saturable processes. The direct addition of fresh lipoprotein-deficient serum to the medium partially reversed the secondary decrease in LDL receptor activity that followed the initial acute increase. Frequent medium changes enhanced the long term rate of activation of the receptor, depleted the cell of cholesterol, and increased the rate of sterol synthesis. These results suggest that regulation of the LDL receptor activity is a potentially rapid process than can respond acutely to changes in the rate of cholesterol flux into or out of the cell.

Cells, Cultured↗
PubMed1980

Platelet-derived growth factor stimulates activity of low density lipoprotein receptors.

Partially purified platelet-derived growth factor stimulates low density lipoprotein binding and degradation in cultured aortic smooth muscle cells of monkeys by increasing the number of available low density lipoprotein receptors. When platelet-derived growth factor was added to quiescent cells, low density lipoprotein binding increased within 4-8 hr. Stimulation of low density lipoprotein receptor activity preceded stimulation of DNA synthesis by platelet-derived growth factor by 8-12 hr. Enhancement of endogenous cholesterol synthesis by platelet-derived growth factor preceded stimulation of low density lipoprotein receptor activity. These findings suggest that the platelet-derived growth factor can increase both the exogenous and endogenous supplies of cholesterol to the cell for its use during cell proliferation.

Animals↗
PubMed1979

High-density lipoprotein-cholesterol in survivors of myocardial infarction.

High-density lipoprotein-cholesterol (HDL-Chol) levels were higher in a group of 83 myocardial infarction survivors who participated in a moderate, graded exercise program (47 +/- 13 mg/dL) than in 103 nonexercising coronary heart disease patients (40 +/- 11 mg/dL, P less than .001), reaching levels undistinguishable from those of 181 population controls (44 +/- 12 mg/dL). The level of exercise and concentration of HDL-Chol were correlated (r = .24, P less than .05). In 18 patients studied longitudinally, HDL-Chol levels increased from 35 +/- 8 mg/dL before participation to 40 mg/dL (P less than .001) after one week, and remained at that level for six months. Concurrently, functional aerobic impairment decreased from 31% +/- 29% to 11% (P less than .01). These observations suggest that participation in a moderate exercise program increases HDL-Chol levels in myocardial infarction survivors and may contribute to lowering the risk for subsequent infarction.

Adult↗
PubMed1979

Increase in lipoprotein lipase during clofibrate treatment of hypertriglyceridemia in patients on hemodialysis.

In 11 hypertriglyceridemic patients on hemodialysis, clofibrate (1 to 1.50 g per week) reduced plasma triglyceride (-40 +/- 20%, P less than 0.001), very-low-density-lipoprotein triglyceride (-44 +/- 20%, P less than 0.001) and very-low-density lipoprotein cholesterol (-39 +/- 25%, P less than 0.01), and it increased high-density-lipoprotein cholesterol (82 +/- 106%, P less than 0.005). Low pretreatment lipoprotein-lipase activity in adipose-tissue specimens and postheparin plasma increased to normal with clofibrate, whereas low hepatic triglyceride lipase activity did not change. The reduced very-low-density-lipoprotein triglyceride correlated with the increased lipoprotein-lipase activity in adipose tissue (rs = 0.792, P less than 0.02, n = 8) and postheparin plasma (rs = 0.851, P less than 0.02, n = 8), whereas increased high-density-lipoprotein cholesterol correlated with changes in this activity in adipose tissue (rs = 0.696, P less than 0.06) and post-heparin plasma (rs = 0.679, P less than 0.10). There was no correlation between changes in hepatic triglyceride lipase activity and plasma lipids during treatment. Reduced lipoprotein-lipase activity may cause hypertriglyceridemia and decreased high-density-lipoprotein cholesterol in patients on hemodialysis; clofibrate may correct these abnormalities by increasing lipoprotein-lipase activity to normal.

Adipose Tissue↗
PubMed1979

Abnormal lipoprotein-lipase-mediated plasma triglyceride removal in untreated diabetes mellitus associated with hypertriglyceridemia.

Hypertriglyceridemia is common in untreated diabetes mellitus. An abnormality in the interaction of lipoprotein lipase with endogenous circulating plasma lipoprotein triglyceride has been demonstrated in untreated diabetes. These diabetics have a decreased maximal removal capacity for plasma triglyceride (27.0 mg TG/kh/hr) and increased Km (390 mg/dl) for endogenous plasma triglyceride-lipoprotein lipase interaction compared to that found in nondiabetic hypertriglyceridemic subjects (Vmax, 32.0; km, 157). Diabetics treated for at least two months have a maximal removal capacity and Km similar to that of nondiabetic subjects (Vmax, 32.7; Km, 192). No evidence for an increase in triglyceride production due to diabetes per se was found. When diabetic subjects with triglyceride levels over 400 mg/dl were selected for study, most were found to have an independent familial form of hypertriglyceridemia.

Adolescent↗
PubMed1979

Reduction of plasma triglyceride concentration by acute stress in man.

Three different forms of stress all resulted in acute reduction of plasma triglyceride concentrations. Pyrogen reactions in two hypertriglyceridemic men resulted in the lowering of very-low-density lipoprotein (VLDL) triglyceride levels by 93% and 73% due to decreased secretion of this lipoprotein into plasma. More modest reductions in plasma triglycerides were observed after 2-deoxyglucose-induced intracellular glucopenia and insulin-induced hypoglycemia. With hypoglycemia, the lowering of plasma triglyceride concentration correlated significantly with the stimulation of urinary epinephrine output (r = 0.86) but with neither the urinary norepinephrine response nor with the increase in plasma immunoreactive glucagon levels. To further test whether these changes in plasma triglyceride levels were mediated via the sympathetic nervous system, hypoglycemia was evoked by insulin in subjects with traumatic spinal cord transactions. Two such subjects, who demonstrated sympathetic stimulation in response to hypoglycemia, had evidence of reduced VLDL secretion into plasma, while in two who had no evidence of an adrenergic response. VLDL secretion was not inhibited. Thus, acute lowering of plasma triglyceride concentrations by certain forms of stress appears to be mediated via the sympathetic nervous system.

Acute Disease↗
PubMed1979

Effect of dietary fructose on triglyceride transport and glucoregulatory hormones in hypertriglyceridemic men.

Effects of dietary fructose on triglyceride metabolism and on basal levels and meal responses of glucose, insulin, and glucagon were studied in six hypertriglyceridemic men, two of whom were also diabetic. Constant composition, weight-maintaining formula diets were used with substitution of fructose for 20% of the carbohydrate calories in both fat-containing (45% carbohydrate) and fat-free (85% carbohydrate) periods; each of the four dietary periods was at least 2 weeks long in every subject. No effect of fructose on fasting levels of triglycerides could be seen in any of the diets. No alterations of triglyceride transport occurred with fructose substitution in the fat-containing diets, but significant reductions of triglyceride transport rates were seen with fructose substitution in the 85% carbohydrate diets using both the heparin infusion lipolytic rate method and the 3H-glycerol methods of assessment of tryglyceride turnover (- 16 and - 21%, respectively). Dietary fructose induced no significant changes in either basal levels or responses during a "formula tolerance test" of glucose, insulin, or glucagon. Thus, dietary fructose given for several weeks does not appear to cause further elevations of plasma triglyceride levels in hypertriglyceridemic men.

Adult↗
PubMed1979

Effect of donor age on the binding and degradation of low density lipoproteins by cultured human arterial smooth muscle cells.

The ability of human arterial smooth muscle cells growing in tissue culture to bind, incorporate and degrade low density lipoproteins (LDL) was studied as a function of cell donor age from 5 to 71 years. LDL binding to cell surface receptors did not change with donor age. However, LDL degradation was significantly decreased in cells from older donors. These results may be relevant to the enhanced accumulation of cellular cholesterol and LDL observed in the aging human artery. Thus, impaired LDL degradation by arterial smooth muscle cells may be one of several factors involved in the accelerated development of atherosclerosis with aging.

Adolescent↗
PubMed1979

Low-density lipoprotein receptor activity in cultured human skin fibroblasts. Mechanism of insulin-induced stimulation.

Low-density lipoproteins (LDL) receptor activity, as reflected by LDL degradation, was stimulated by the addition of insulin to cultures of human skin fibroblasts. These changes occurred independently of the glucose concentration of the incubation medium and occurred whether or not LDL receptor activity was suppressed. A comparison of the saturation kinetics of LDL receptor activity in the presence and absence of insulin indicated that insulin produced a 35% increase in Vmax with no difference in "apparent Km". These results suggest that insulin enhances LDL receptor activity by increasing the number of LDL receptors rather than by influencing binding affinity. In confirmation, LDL degradation by receptor negative cells was not enhanced by insulin. Sterol synthesis from [14C]acetate was also stimulated by insulin, but egress of cholesterol and cellular cholesterol content were unaffected by the hormone. The effect of insulin on LDL receptors was not dependent on its known ability to enhance cellular DNA synthesis and proliferation, because insulin stimulated LDL receptor activity in cells kept quiescent by maintenance in plasma-derived serum that was devoid of platelet derived growth factor. Nevertheless, the effect of insulin in enhancing LDL receptor number, coupled with stimulation of endogenous cholesterol synthesis, provides a mechanism whereby the cell could theoretically increase its supply of cholesterol during times of additional need.

Animals↗
PubMed1979

Regulatory role of triiodothyronine in the degradation of low density lipoprotein by cultured human skin fibroblasts.

Degradation of [125I]-labeled low density lipoprotein (LDL) by cultured normal human skin fibroblasts was enhanced by exposure to concentrations of L-triiodothyronine (T3) spanning the physiological range. Analysis of LDL concentration curves suggests that T3 may increase LDL receptor number rather than alter the affinity of LDL for its receptor. No effect of T3 on LDL degradation was observed in receptor negative cells. Thus thyroid hormone appears to regulate receptor-mediated LDL degradation by increasing the binding of the lipoprotein to its cell-surface receptor.

Cells, Cultured↗
PubMed1979

Low density lipoprotein receptor activity in fibroblasts cultured from diabetic donors.

Low density lipoprotein (LDL) receptor activity was evaluated in cultured skin fibroblasts from diabetics and nondiabetic controls to evaluate whether intrinsic abnormalities of the LDL pathway exist, which might account for the premature atherosclerosis associated with diabetes mellitus. LDL receptors did not differ between cells grown from 16 diabetics (7 insulin-dependent, 9 non-insulin-dependent ) or from 16 nondiabetic controls. An inverse relationship between LDL receptor activity and cell density was observed (y = 1.35x-1.22, r = 0.90, P less than 0.001), which appeared the same for diabetic and nondiabetic cells. Normalized values for LDL degradation by diabetic and nondiabetic cell strains were 1.52 +/- 0.42% of added LDL/10(6) cells and 1.34 +/- 0.28, respectively (P = NS). The kinetics of the LDL receptor also appeared to be the same in cells derived from a diabetic and a nondiabetic donor. LDL receptor activity in diabetic cells increased appropriately in response to physiologic concentrations of insulin in the incubation mediu. Thus, LDL receptor activity appears to be normal in diabetic cell strains. Therefore, these results do not support the possibility that alterations in the LDL pathway contribute to the accelerated atherosclerosis associated with diabetes.

Adult↗