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K Y Lei

Publications and source records attributed to K Y Lei.

At least 37 records · Page 2Linked to original sources
PubMed1992

Lipid composition and fluidity of the erythrocyte membrane in copper-deficient rats.

The influence of dietary copper on lipid composition, phospholipid fatty acid and protein profiles and fluidity of the erythrocyte membranes of rats is reported. In general Cu deficiency in rats induced some changes in the phospholipid-fatty acid profile of erythrocyte membranes when compared with Cu-adequate animals. Stearic (18:0) and docosadienoic (22:2n-3) acids contents, for example, were significantly increased (P < 0.001) while oleic (18:1n-9) and linolenic (18:3n-3) acid contents were significantly depressed (P < 0.001) as a result of Cu deficiency. Moreover the cholesterol:phospholipids molar ratio and the cholesterol (mol):membrane proteins (mg) ratio in Cu-deficient rats were, to different degrees, significantly lower than in animals fed on Cu-adequate diets. In addition, diets deficient in Cu led to a reduction in erythrocyte membrane fluidity (P < 0.001) as assessed by the intramolecular excimer fluorescence of 1,3-di(1-pyrenyl) propane. However, no significant alteration in the phospholipid:protein ratio was observed as a result of differences in dietary treatment. The pattern of erythrocyte membrane proteins obtained with sodium dodecyl sulphate-polyacrylamide gel electrophoresis did not seem to be influenced by Cu-deficient diets.

Animals↗
PubMed1992

Copper deficiency alters plasma pool size, percent composition and concentration of lipoprotein components in rats.

Forty weanling male Sprague rats were randomly assigned to two dietary treatments, copper-deficient (9.0 mumol/kg diet) and copper-adequate (102.2 mumol/kg diet). After 7 wk of treatment, reductions in body weight and hematocrit, and an increase in relative heart weight, were observed in the copper-deficient rats. Plasma VLDL, LDL and HDL were isolated by ultracentrifugation and Sepharose column chromatography. In copper-deficient rats, the percent composition of protein was reduced by one-half, and triglyceride was increased by 1.6- and 2.7-fold in LDL and VLDL fractions, respectively. In VLDL, the marked increase in triglyceride was compensated by at least a 75% decrease in percent composition of cholesterol and phospholipids as a result of copper deficiency. No treatment difference in percent composition of HDL components was detected. When the data were expressed as the amount present in the vascular pool corrected for body weight, the plasma pool size of protein, triglyceride, phospholipid and cholesterol of LDL and HDL were increased twofold or more by copper deficiency. In VLDL, a sixfold increase in triglyceride, a 36% reduction in cholesterol, and no change in phospholipid and protein pool size were observed in copper-deficient rats. These data suggest that copper deficiency may enlarge the particle size but not particle number of VLDL, increase both particle size and number of LDL, and elevate particle number but not size of HDL.

Animals↗
PubMed1991

Locating a low density lipoprotein-targeting domain of human apolipoprotein B-100 by expressing a minigene construct in transgenic mice.

Through its interaction with the low density lipoprotein (LDL) receptor, apolipoprotein (apo) B-100 is a major determinant of LDL metabolism and plasma cholesterol. Its receptor binding ability is conformation-dependent and requires its expression on the right lipoprotein particles. The structural signal that targets apoB-100 to LDL is unknown. We have microinjected a human apoB-100 minigene construct comprising less than 25% of the apoB-100 sequence driven by the natural apoB promoter to produce transgenic mice. The transgene product was expressed at a high level and was present exclusively in the LDL of these animals. Analysis of the responsible sequence (residues 2878-3925 of apoB-100) reveals unique structural features that may be important in its role as an LDL-targeting domain.

Animals↗
PubMed1991

Incorporation of tritiated water into sterol in copper-deficient rats.

The effect of copper deficiency on absolute rates of cholesterol synthesis was investigated in the rat. Male weanling rats were fed semi-purified diets containing adequate (7.13 ppm) or deficient (0.621 ppm) levels of copper for 6 weeks. Copper-adequate and -deficient animals (n = 6/group) were injected intraperitoneally with 50 mCi 3H-labelled water and killed 1 h post-injection. Copper-deficient animals had elevated heart weights and reduced body and spleen weights. Plasma cholesterol levels were significantly elevated and hematocrits were reduced. Absolute rates of carcass cholesterol synthesis per organ were 1.9-fold higher in copper-deficient rats (P less than 0.025). Previous studies have indicated that hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (E.C.1.1.1.34) activity is increased by copper deficiency; however, de novo synthesis of cholesterol from 3H-labelled water was not significantly elevated in the liver. The present data indicate that newly synthesized cholesterol exported to the plasma was increased 2.1-fold (P less than 0.01) in copper-deficient rats. Since it has been demonstrated that hepatic export of cholesterol is increased with copper deficiency and that the major tissue for export of newly synthesized cholesterol is the liver, we hypothesize that the origin of radiolabeled cholesterol in the plasma was the liver. These data support the hypothesis that elevated levels of hepatic HMG-CoA reductase seen with copper deficiency are associated with an increased rate of whole body and hepatic cholesterol synthesis.

Animals↗
PubMed1991

Copper deficiency and hyperlipoproteinemia induced by a tetramine cupruretic agent in rabbits.

The effectiveness of a cupruretic agent, N,N'-bis-(2 amino ethyl)-1,3-propanediamine HCl or 2,3,2-tetramine HCl (TETA), in the induction of copper (Cu) deficiency and the ability of a Cu-deficient diet in the maintenance of the depressed Cu status 10 wk after TETA treatment were examined in this study. In the first experiment, 42 male New Zealand White rabbits, 35 d of age, were randomly divided into three dietary treatments: a copper (Cu)-deficient (2.3 mg Cu/kg diet), a Cu-adequate (13.5 mg Cu/kg diet), and a commercial ration (21.6 mg Cu/kg diet) group. A single oral dose of 100 mg of 2,3,2-tetramine HCl TETA/kg body wt/d were administered to half of the rabbits from each treatment group for 10 d while the remaining rabbits were untreated. In the second experiment, 10 similar rabbits were assigned to three treatments: Cu-deficient plus TETA (n = 4); Cu-adequate plus TETA (n = 3); and Cu-adequate alone (n = 3). The rabbits were fed a TETA dose of 100 mg/d for three 4-d periods over 3 wk, and thereafter maintained on the diets for another 10 wk. Rabbits from the first experiment fed Cu-deficient diet and treated with TETA demonstrated cardiac hypertrophy and markedly reduced plasma and liver Cu concentrations that indicated that the animals were Cu-deficient. Significant elevations (twofold) in low density lipoprotein (LDL) protein, cholesterol, triglyceride, and apolipoprotein B (apo B) concentrations were observed in TETA treated rabbits fed Cu-deficient diet. In the second experiment, the plasma LDL protein level remained elevated, the plasma Cu level was reduced 45%, and the Cu level of the heart when expressed as microgram/g dry tissue was reduced, 10 wk post TETA treatment in rabbits maintained on Cu-deficient diet. Thus, Cu deficiency and hyperlipoproteinemia was rapidly induced by TETA and was still evident 10 wk posttreatment in rabbits maintained on a Cu-deficient diet.

Animals↗
PubMed1991

Copper uptake and retention in liver parenchymal cells isolated from nutritionally copper-deficient rats.

Copper uptake and retention were studied in primary cultures of liver parenchymal cells isolated from copper-deficient rats. Male Sprague-Dawley rats were fed a copper-deficient diet (less than 1 mg Cu/kg) for 10 wk. Copper-deficient rats were characterized by low copper concentrations in plasma and liver, anemia, low plasma ceruloplasmin oxidase activity and increased 64Cu whole-body retention. Freshly isolated liver parenchymal cells from copper-deficient rats showed a higher 64Cu influx, which was associated with a higher apparent Vmax of 45 +/- 4 pmol Cu.mg protein-1.min-1 as compared with 30 +/- 3 pmol Cu.mg protein-1.min-1 for cells isolated from copper-sufficient rats. No significant difference in the apparent Km (approximately 30 mumol/L) was observed. Relative 64Cu efflux from cells from copper-deficient rats was significantly smaller than the efflux from cells from copper-sufficient rats after prelabeling as determined by 2-h efflux experiments. Analysis of the medium after efflux from cells from copper-deficient rats showed elevated protein-associated 64Cu, suggesting a higher incorporation of radioactive copper during metalloprotein synthesis. Effects of copper deficiency persist in primary cultures of parenchymal cells derived from copper-deficient rats, and short-term cultures of these cells offer a prospect for the study of cell biological aspects of the metabolic adaptation of the liver to copper deficiency.

Animals↗
PubMed1990

High-density lipoprotein cholesteryl ester and protein catabolism in hypercholesterolemic rats induced by copper deficiency.

High-density lipoprotein (HDL) catabolism induced by copper deficiency was examined in vivo in hypercholesterolemic Sprague-Dawley rats. Doubly labeled HDL was used to trace the catabolic pathways of both cholesteryl ester and protein moieties of HDL particles. The catabolic rate of removal from the plasma, as well as uptake by various tissues, was determined for each HDL component. Copper-deficient rats exhibited a 30% increase in HDL cholesterol concentration, confirming hypercholesterolemia. In addition, plasma volume was enlarged 38% in deficient animals, resulting in a significantly increased intravascular pool of all HDL components of at least 60%. These data emphasize the importance of determining plasma volume and total pool size of pertinent plasma components in this hypercholesterolemic model. The absolute catabolic rate (ACR) of HDL protein removal from the plasma was 369 +/- 22 and 278 +/- 12 micrograms/h in copper-deficient and control rats, respectively. The ACR of HDL cholesteryl ester was 647 +/- 37 micrograms/h in deficient animals and 321 +/- 13 micrograms/h in controls, suggesting that the mechanisms of selective clearance of HDL cholesteryl ester (compared with protein) were increased threefold by copper deficiency. Virtually all of the increased removal of HDL cholesteryl ester in deficient rats occurred in the liver. Since previous studies indicate that increased hepatic cholesterol excretion may not occur in copper deficiency, the present results suggest that cholesterol delivered to the liver as HDL cholesteryl ester is possibly reassembled into new HDL particles at an increased rate in copper-deficient rats.

Animals↗
PubMed1990

Specific binding and uptake of apolipoprotein E-free high density lipoproteins by cultured liver parenchymal cells of copper-deficient rats.

The influence of copper deficiency on the binding and uptake of apolipoprotein E-free high density lipoprotein (apo E-free HDL) in cultured rat hepatic parenchymal cells was examined in this study. Male weanling Sprague-Dawley rats were randomly divided into two treatments, a Cu-adequate (7.33 mg Cu/kg diet) or a Cu-deficient (1.04 mg Cu/kg diet) group. After 7 weeks, plasma apo E-free HDL were isolated by a combination of ultracentrifugation, gel filtration, and heparin-Sepharose affinity chromatography. Parenchymal cells were isolated from collagenase perfused liver of Cu-deficient and adequate rats and cultured for 16 hours at 37 degrees C prior to incubation with iodinated apo E-free HDL from the same treatment group. Cells were incubated with 5 microg/ml(125) I-apo E-free HDL for 2, 6, or 12 hours in the presence or absence of 200 microg/ml (40-fold) excess unlabeled apo E-free HDL. Increases in specific binding at 4 degrees C and specific cell-associated uptake at 37 degrees C as a function of time were observed with cells and HDL from Cu-deficient rats. Cells were also incubated for 6 hours with 8 concentrations of (125)I-apo E-free HDL in the presence or absence of excess unlabeled HDL. Although no significant increase in specific binding was detected at 4 degrees C as a function of ligand concentration, the response tended to be higher at 5 to 15 microg HDL/ml for the Cu-deficient treatment. However, at 37 degrees C the specific cell-associated uptake was increased markedly with cells and HDL from Cu-deficient rats. The observed increases in HDL binding and uptake indicate that these processes may be enhanced in Cu-deficient rats. These data are also consistent with recent in vivo results which indicate that plasma clearance and tissue uptake of HDL are increased in Cu-deficient rats.

Journal Article↗
PubMed1990

The effect of copper deficiency on rat hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase activity.

The effect of copper deficiency on hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase, the key enzyme regulating cholesterol biosynthesis, was investigated in the rat. Male weanling rats were fed semipurified diets containing adequate, marginal, or deficient levels of copper for 6 weeks. Two separate studies were conducted; in the first study, animals were fasted 12 hours prior to analysis and in the second study, animals were fed diets ad libitum. Plasma lipid levels, hepatic cholesterol concentrations, and 3-hydroxy-3-methylglutaryl coenzyme A reductase specific activity, total and active, were determined. Consistent with previous findings, plasma total cholesterol and triglyceride levels were significantly elevated in copper-deficient rats. Copper deficiency resulted in a significant decrease in hepatic total cholesterol levels. Total and active levels of 3-hydroxy-3-methylglutaryl coenzyme A reductase in fed animals were elevated twofold with copper deficiency, with the active form of the enzyme constituting approximately 30% of total activity. 3-Hydroxy-3-methylglutaryl coenzyme A reductase activity in copper-deficient fasted rats was twofold higher than for the fasted adequate animal; however, fasting did result in a 10-fold reduction in hepatic reductase specific activity. These data support the hypothesis that copper deficiency results in a hypercholesterolemic state in the rat associated with increased hepatic cholesterol synthesis.

Journal Article↗
PubMed1989

In vivo apoprotein catabolism of high density lipoproteins in copper-deficient, hypercholesterolemic rats.

High density lipoprotein (HDL) apoprotein catabolism was examined in male Sprague-Dawley rats deficient in dietary copper. Twenty-four rats were randomly divided into two groups: copper-adequate (control, 5 mg of copper/kg diet) and copper-deficient (0.6 mg of copper/kg diet). After 5 weeks, animals were administered a tracer dose of iodinated HDL protein previously isolated from donor rats that were subjected to the same dietary treatments as the test animals. Copper-deficient rats exhibited a 54% increase in plasma volume and a 26% increase in HDL protein concentration above controls. Consequently, the intravascular pool of total HDL protein was increased 2-fold. The fractional catabolic rate of total HDL protein was similar between groups. However, because of the increased intravascular HDL pool in copper-deficient animals, the absolute catabolic rate was greater (640 +/- 49 micrograms/hr vs 316 +/- 12 micrograms/hr in controls). Tissue uptake of total HDL protein in copper-deficient rats tended to be greater in the kidneys, spleen, and testes compared with controls; the heart exhibited a significant 2.3-fold increase. In contrast, the catabolic rate of HDL protein in the liver and adrenal gland were not different between treatment groups. That an obligatory increase in HDL protein uptake was not observed in the liver and adrenal gland (organs which are sensitive to and can further metabolize cholesterol) suggests that these organs may be regulated, possibly contributing to the observed hypercholesterolemia in this model. These data imply that total HDL apoprotein catabolism is increased in response to the increased intravascular pool of HDL in copper-deficient rats.

Animals↗
PubMed1988

Apolipoprotein E-rich HDL binding to liver plasma membranes in copper-deficient rats.

Copper deficiency in rats raises plasma cholesterol concentration while reducing live cholesterol concentration. One consequence of this cholesterol redistribution is the accumulation of a large high-density lipoprotein (HDL) particle rich in apolipoprotein E (apo E). The purpose of this study was to determine, using an in vitro binding assay, if the interaction of apo E-rich HDL with hepatic lipoprotein binding sites may be affected by copper deficiency. Male Sprague-Dawley rats were divided into two dietary treatments (copper-deficient and -adequate) and placed on a dietary regimen for 8 weeks. Subsequent to exsanguination, hepatic plasma membranes were prepared and apo E-rich HDL was isolated from rats of each treatment by ultracentrifugation, agarose column chromatography, and heparin-Sepharose affinity chromatography. Total binding and experimentally derived specific binding of 125I-apo E-rich HDl to hepatic plasma membranes indicated greater binding when lipoproteins and membranes from copper-deficient animals were used in the assay compared to controls. Scatchard analysis of specific binding data indicated that equilibrium binding affinity (Kd) was also affected by copper deficiency. The hepatic binding sites recognizing apo E-rich HDL were not affected by EDTA or pronase, of relatively high capacity, and recognized a variety of other rat lipoproteins.

5'-Nucleotidase↗
PubMed1988

Alterations in lipid composition and fluidity of liver plasma membranes in copper-deficient rats.

In view of the importance of membrane fluidity on cell functions, the influence of phospholipid acyl groups on membrane fluidity, and the changes in lipid metabolism induced by copper (Cu) deficiency, this study was designed to examine the influence of dietary Cu on the lipid composition and fluidity of liver plasma membranes. Male Sprague-Dawley rats were divided into two dietary treatments, namely Cu deficient and Cu adequate. After 8 weeks of treatment, liver plasma membranes were isolated by sucrose density gradient centrifugation. The lipid fluidity of plasma membranes, as assessed by the intramolecular eximer fluorescence of 1,3-di(1-pyrenyl) propane, was significantly depressed by Cu deficiency. In addition, Cu deficiency significantly reduced the content of arachidonic and palmitoleic acids but increased the docosatetraenoic and docosahexaenoic acids of membrane phospholipids. This alteration in unsaturated phospholipid fatty acid composition, especially the large reduction in arachidonic acid, may have contributed to the depressed membrane fluidity. Furthermore, Cu deficiency also markedly altered the fatty acid composition of the triacylglycerols associated with the plasma membranes. Thus, the lipid composition and fluidity of liver plasma membranes are responsive to the animal's Cu status.

Animals↗
PubMed1987

Lipoprotein receptors in copper-deficient rats: apolipoprotein E-free high density lipoprotein binding to liver membranes.

Twenty-four male weanling Sprague-Dawley rats were randomly and equally divided into two dietary treatments, copper-deficient and adequate (0.7 mg and 8.0 mg Cu/kg diet, respectively). Deionized water and diet were provided ad libitum. After 8 weeks, rats were exsanguinated, membranes prepared from livers, and plasma high density lipoproteins (HDL) isolated by ultracentrifugation and agarose column chromatography. Heparin-sepharose affinity chromatography was used to isolate subfractions of HDL devoid of apolipoprotein E (apo E-free HDL). The apo E-free HDL derived from rats of each dietary treatment were iodinated and bound to liver membranes prepared from rats of both treatment groups. Total binding data, specific binding data, and computer derived estimates of maximum equilibrium binding (Bmax) indicate less binding was observed when lipoproteins and membranes from copper-deficient animals were used in the binding assay compared to controls. In addition, a 2 X 2 factorial analysis of binding parameters derived from all experiments demonstrated a significant lipoprotein effect, indicating the reduction in binding may be associated with apo E-free HDL obtained from copper-deficient rats. The present findings suggest a reduction in binding of apo E-free HDL to their binding sites may contribute to the hypercholesterolemia and hyperlipoproteinemia observed in copper deficiency.

Animals↗
PubMed1987

Effect of long-term oral contraceptive therapy before pregnancy on maternal and fetal zinc and copper status.

Thirteen pregnant women who conceived within six months after terminating oral contraceptive agent therapy of at least three years' duration participated in this study. Nine pregnant women with no history of oral contraceptive agent use served as controls. At delivery, erythrocyte counts were reduced, and during the first trimester and at delivery mean corpuscular hemoglobin and volume values were increased and erythrocyte zinc values were reduced in the oral contraceptive agent group as compared with controls. These changes appeared to be subclinical in magnitude and oral contraceptive agents may have induced a macrocytic erythrocyte population. Because no changes in maternal plasma zinc and copper levels were observed and no hematologic, biochemical, or anthropometric differences were observed in neonates, long-term oral contraceptive agent usage appeared to have little or no effect on zinc and copper metabolism in a subsequent pregnancy.

Adolescent↗
PubMed1986

Alterations in lipid and protein profiles of plasma lipoproteins in middle-aged men consequent to an aerobic exercise program.

Thirty-four healthy, untrained middle-aged males (mean = 58.2 years) volunteered for a longitudinal study investigating alterations in lipoprotein profiles consequent to 20 weeks of aerobic training. Twenty randomly selected experimental subjects (E) participated in a walk/run training program 3 d/wk, 48 min/d, at an intensity equal to 65% to 85% of their heart rate reserve, while 14 control subjects (C) remained in an untrained state. Blood samples were obtained in the morning after a 14-hour fast. Plasma lipoproteins were separated by ultracentrifugation and agarose-column chromatography into very low (VLDL), low (LDL), and high (HDL) density lipoprotein fractions. A training effect was evidenced in E by significant increases (P less than 0.001) in absolute VO2 max (15.2%) and relative VO2 max (16.8%). Dietary composition was monitored pretraining and posttraining with no significant change seen in either E or C. Alterations in the lipoprotein profile of E included a significant increase in HDL-cholesterol (16.6%) and significant reductions in VLDL-cholesterol (72.1%), LDL-triglyceride (26.5%), VLDL-protein (33.5%), and LDL-protein (18.7%). Furthermore, no significant changes in the level of HDL-protein and apolipoprotein AI in the HDL fraction were observed in either E or C. These data suggest that aerobic training can significantly increase HDL-cholesterol and alter lipoprotein profiles, which may subsequently reduce the risk of coronary artery disease.

Cholesterol↗
PubMed1986

Aging and dietary influences on plasma lipoproteins and apolipoproteins in nonhuman primates.

Nineteen young (3 to 4-years-old), 25 adult (8 to 14-years-old), and 22 aged (18 years and older) pig-tailed macaques (Macaca nemestrina) were fed a semipurified control diet stringent in fat, cholesterol, refined sugar, and sodium for six months. Each group was almost equally divided by sex. Thereafter, half of each age group was fed a test diet high in fat (41% of calories), cholesterol (865 mg/kg), sodium, and refined sugar, while the rest consumed the control diet. After three years of dietary treatment, plasma and blood volumes were determined and fasting blood samples were collected for lipoprotein analysis. The protein content of very low density lipoproteins (VLDL) was increased in the test animals as compared to the controls. In general, low density lipoprotein (LDL) cholesterol, protein, and apolipoprotein B-100 values were markedly elevated by the test diet. However, these elevations were mainly confined to the young and adult groups, with little or no increases observed in the old group. The test diet also induced small but significant increases in high density lipoprotein (HDL) cholesterol, protein, and apolipoprotein A-I values. In addition, HDL cholesterol and protein values were higher in young females than males, whereas this trend was not observed in adults.

Aging↗
PubMed1985

Dexamethasone and zinc in combination inhibit the anchorage-independent growth of S-91 Cloudman murine melanoma.

Zinc inhibited the colony formation of Cloudman S-91 murine melanoma cells in a dose dependent manner with an ID50 of 3.4 ug/ml. Total inhibition of the melanoma colony-forming units occurred at a zinc concentration of 4.42 ug/ml. In the presence of dexamethasone the ID50 for zinc inhibition was reduced by 49% and total inhibition of anchorage-independent growth occurred at the achievable in vivo zinc concentration of 3.0 ug/ml. Dexamethasone and zinc in combination effected a greater than additive inhibition of the murine melanoma colony-forming units. Statistical evaluation of these results showed that zinc and dexamethasone interacted synergistically to inhibit the formation of murine melanoma colonies.

Animals↗