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1.
Nicotine, a major component of cigarette smoke, plays an important role in the development of cardiovascular disease and lung
cancer in smokers. The effect of nicotine on lipoprotein metabolism was studied using rats as the experimental animal. There
was a significant increase in the total cholesterol, phospholipids, and triglycerides as well as the amount of lipids associated
with very low density lipoprotein (VLDL) and low density lipoprotein (LDL) in sera of nicotine-treated rats. The incorporation
of 3H labeled leucine into the apo B was found to be increased both in the medium and associated cells in the hepatocytes isolated
from nicotine-treated rats indicating an increased synthesis and secretion of the apo B containing lipoproteins. This was
further confirmed by the higher incorporation of 14C acetate into total and individual lipids of LDL and VLDL secreted into the medium as well as that associated with different
lipids in the cell layer. The activity of lipoprotein lipase in extrahepatic tissues and plasma lecithin cholesterol acyltransferase
activity were significantly lower in nicotine-treated rats. These results indicate that nicotine exerts hyperlipidemic effects
particularly by increasing the synthesis and secretion of triglyceride-rich lipoproteins. Since nicotine is one of the major
hazardous components present in cigarette smoke and tobacco, one can extrapolate that the deleterious effect exerted by nicotine
on rats extends to cigarette smokers and those who use other forms of tobacco. 相似文献
2.
K. Ananth Narayan 《Lipids》1970,5(1):156-158
The incorporation of U-14C-leucine into five classes of serum lipoproteins and into lipoprotein-free serum proteins was investigated in partially hepatectomized,
sham operated and normal rats. The serum concentration of very low density lipoprotein and the predominant subfraction of
high density lipoprotein (HDL2) was considerably reduced in partially hepatectomized rats as compared with both normal and sham operated rats. The incorporation
of U-14C-leucine into HDL2 of partially hepatectomized rats was only one third and one fourth of that observed with normal and sham operated rats, respectively.
On the other hand, the incorporation of the label into low density lipoproteins and into serum proteins was slightly greater
in partially hepatectomized rats as compared with normal rats. In sham operated animals, the incorporation into most fractions
was considerably greater than those observed with lobectomized and normal rats. 相似文献
3.
Rat lung slices were used to examine the net uptake of pyruvate and the incorporation of specifically labeled pyruvate-14C into CO2 and lipid fractions. Pyruvate uptake and pyruvate-2-14C incorporation into these fractions was increased by raising the pyruvate concentration in the incubation medium from 1 to
25 mM. The addition of 5 mM glucose to the incubation medium decreased the apparent oxidation of pyruvate-2-14C to CO2 but increased its incorporation into lung lipids. Glucose did not increase net pyruvate uptake by lung slices. The incorporation
of pyruvate-1-14C and pyruvate-3-14C into CO2 and lung lipids was also examined. The results indicated that a major portion of the pyruvate utilized was oxidized to CO2 with substantial levels found in the fatty acid moiety of lung phospholipids. The low level of pyruvate conversion to phospholipid
glycerol, possibly via the dicarboxylic acid shuttle, is of uncertain physiological significance.
Journal Series Paper No. 4258 of the Agricultural Experiment Station, Pennsylvania State University. 相似文献
4.
Vitamin E has no known plasma carrier protein and is transported by plasma lipoproteins. The site of association of vitamin
E in the lipoprotein particle and the mode of transfer of vitamin E between plasma lipoproteins have not been ascertained.
Since neutral lipids (triglycerides and cholesterol esters) exchange between plasma lipoproteins by processes mediated by
neutral lipid transfer protein, we questioned that if vitamin E, a hydrophobic molecule, is carried in the core of the lipoprotein
particle then its transfer between plasma lipoproteins may be mediated by neutral lipid transfer protein. Transfer of D-α(5-methyl-3H)tocopherol from in vitro-labeled human plasma lipoprotein fractions to other plasma lipoproteins was measured under incubation
conditions that were designed to yield markedly differing degrees of neutral lipid exchange. Despite the presence of the d>1.21
g/ml lipoprotein-poor plasma fraction or purified lipid transfer protein that resulted in up to a 10-fold increase in neutral
lipid transfer, vitamin E transfer between very low density lipoproteins, low density and high density lipoproteins remained
constant. Even excess amounts of lipid transfer protein, which caused triglyceride transfer between very low density and high
density lipoproteins to reach saturation, failed to affect significantly vitamin E transfer. Vitamin E distribution between
lipoprotein fractions did correlate with lipoprotein mass ratios. Vitamin E transfer was higher as the protein ratio of acceptor
lipoproteins to donor lipoproteins increased. We conclude that vitamin E transfer between lipoproteins is not dependent primarily
on neutral lipid transfer protein and is not mediated via neutral lipid transfer. 相似文献
5.
Free cholesterol of plasma low density lipoproteins (LDL) and high density lipoproteins (HDL) of the rat was high and that
of plasma very low density lipoproteins (VLDL) was low during the dark period of the diurnal cycle. Variations in the esterified
plasma sterols were inconsistent. Free methyl sterols were high in all lipoproteins during the dark phase. Simultaneously,
the incorporation of14C-acetate into nonsaponifiable sterols and the concentrations of free methyl sterols and cholesterol in the liver were elevated. 相似文献
6.
The influence of dietary restriction on cholesterol transport and metabolism was investigated in rabbits given standard or
cholesterol-rich diets (0.2 g cholesterol/kg body weight daily) eitherad libitum or with 50% caloric ration. Dietary restriction which has only a slight influence in control rabbits markedly aggravated
the disturbances induced by exogenous cholesterol. With limited feeding, control rabbits presented a moderate increase in
plasma cholesterol, whereas marked aggravation of hypercholesterolemia was observed in cholesterol-fed rabbits. Analysis of
the lipoprotein profile showed that the excess of plasma cholesterol with the restricted cholesterol-rich diet corresponded
to an increase in the concentration of very low density lipoprotein (VLDL) and low density lipoproteins (LDL) without any
additional changes in the composition of these lipoproteins. No significant change appeared in the high density lipoprotein
(HDL) concentration. The parameters of cholesterol metabolism were determined, from the curves of [3H] cholesterol radioactivity decrease, using a two-pool model. The increase in cholesterol turnover rate induced by the cholesterol-rich
diet was accentuated by dietary restriction, whereas rabbits on standard restricted diet showed a slight decrease. The large
increase in the size of both pools A and B in cholesterol-fed rabbits was even more pronounced with limited feeding. Dietary
restriction induced additional accumulation of cholesterol in the aortic wall and the grade of the lesions was also aggravated. 相似文献
7.
Roberte Aubert Dominique Perdereau Micheline Roubiscoul Jeannine Herzog Daniel Lemonnier 《Lipids》1988,23(1):48-54
The serum lipid contents of a number of inbred and congenic strains of mice were measured. There were interstrain variations
in each of the lipid fractions in mice fed a normal diet. Male and female C3H mice had the highest total cholesterol level;
AKR mice showed the lowest values. Serum phospholipids were correlated well with cholesterolemia. The greatest variations
between strains were in the triglyceride levels. There also was significant variation in the high density lipoprotein cholesterol
serum levels (from 73–88% of the total cholesterol). The response to a hypercholesterolemic diet (1% cholesterol) was tested
in seven inbred strains. All strains showed changes in serum cholesterol and in the proportions of the lipoproteins fractions.
There was a large increase in the low density lipoprotein+very low density lipoprotein fractions. Feeding the diet revealed
marked interstrain differences in the responses of the serum cholesterol and electrophoretic lipoprotein profiles. The C57BL/6
and B10.D2 strains were hyperresponders to the hypercholesterolemic diet with 71% and 63% of their serum cholesterol in the
low density lipoprotein plus very low density lipoprotein fractions, respectively. 相似文献
8.
The incorporation of L-4,5-[3H]leucine into the ultracentrifugally separated apolipoproteins of very low, low, and high density lipoproteins (VLDL, LDL,
HDL) and into serum albumin was found three-to four-fold higher in nephrotic than in normal rats one hour after intravenous
injection. Incorporation of leucine into the circulating lipids was negligible. Increases of similar magnitude were obtained
in the incorporation of simultaneously injected 1,5[14C] citrate into the lipids of VLDL, LDL, and HDL of nephrotic rats. Of the citrate carbons incorporated into serum and liver
lipids, the proportion in cholesterol was higher in nephrotic rats when compared to normal rats. The incorporation of both
precursors into total proteins and lipids of the liver vs. the incorporation into the lipoproteins was relatively lower in
nephrotic than in control rats, indicating a preferential channeling into secretable products. The occurrence of enhanced
new lipid synthesis in nephrosis was corroborated by the finding of markedly enhanced synthesis of lipoprotein-borne fatty
acids and cholesterol from3H2O. These results point out that while leucine is not an efficient in vivo precursor of lipoprotein lipids in nephrosis, de
novo lipogenesis proceeds from other precursors. Similar trend of changes, though of smaller magnitude, was elicited in rats
after double plasmapheresis, 18 hr apart, when measured 3 hr after the second plasma withdrawal. This indicates that the loss
of circulating proteins either by direct removal or through kidney lesion stimulates the compensatory hepatic response involving
excessive lipoprotein synthesis. Time-course studies showed that peak incorporation of leucine and citrate into the protein
and lipid components of lipoproteins, respectively, as well as into serum albumin, occurred coincidentally 3 hr after the
second plasmapheresis, suggesting an interdependence of the enhanced protein and lipid synthesis. 相似文献
9.
Hideki Shige Toshitsugu Ishikawa Michio Suzukawa Masato Nishiwaki Takeshi Yamashita Kei Nakajima Toshimitsu Ito Kenji Higashi Makoto Ayaori Atsushi Yonemura Paul Nestel Haruo Nakamura 《Lipids》1998,33(12):1169-1175
The effects of vitamin E on cholesteryl ester (CE) metabolism in 1774 cells were examined. Pretreatment of 1774 cells with
vitamin E at concentrations above 50 μM significantly decreased acetylated low density lipoprotein (LDL)-induced incorporation
of [14C]oleate into CF in cells in a dose-dependent manner. This was partly due to vitamin E Also significantly inhibiting the uptake
of [3H]CE-labeled acetylated LDL by 1774 cells. A trend existed toward suppression of acyl-CoA:cholesterol acyltransferase (ACAT)
activity in the cell lysate at high vitamin E concentration, but there was no effect on hydrolysis of CE. These data indicate
that vitamin E reduces the uptake of modified LDL and suppresses ACAT activity, resulting in less cholesterol esterification
in macrophages; a novel mechanism underlying the antiatherogenic properties of vitamin E. 相似文献
10.
Effect of chronic glucagon administration on lipoprotein composition in normally fed,fasted and cholesterol-fed rats 总被引:2,自引:0,他引:2
Catherine Guettet Najmuddin Rostaqui Denis Mathe Bernard Lecuyer Nicole Navarro Bernard Jacotot 《Lipids》1991,26(6):451-458
Male adult Wistar rats received daily (at 9 a.m. and 5 p.m.) 10 μg of zinc-protamine glucagon by subcutaneous injection for
8 days. Plasma cholesterol levels were decreased by 36% in fed rats, 33% in cholesterol-fed rats and by 55% in fasted rats.
Lipoproteins were separated into 22 fractions by ultracentrifugation using a density gradient. Glucagon administration decreased
the cholesterol content in all lipoproteins except low density lipoprotein (LDL1) (1.006–1.040) and very low density lipoprotein (VLDL) from cholesterol-fed rats. The main decrease (−57 to −81%) was observed
in 1.050–1.100 g/mL lipoproteins (LDL2 and HDL2), which contained a large amount of apo E, while HDL3 cholesterol was not affected. Triacylglycerol levels were decreased only in chylomicrons and VLDL (−70%) of fed and cholesterol-fed
rats, while plasma and lipoprotein triacylglycerol levels were not changed in fasted rats treated with glucagon. In normally
fed rats glucagon administration increased by 42% the fractional catabolic rate of [125I]HDL2 while the absolute catabolic rate appeared to be unchanged. Glucagon seems to be a potent hypolipidemic agent affecting mainly
the apo E-rich lipoproteins. Its chronic administration limits lipoprotein accumulation which occurs upon cholesterol feeding. 相似文献
11.
Murthy Akula R. K. Maguire James H. Alphin Robert S. Day Patricia A. Hall Iris H. 《Lipids》1986,21(10):617-622
Three- and 4-phenyl-piperidine-2,6-dione derivatives were investigated for hypolipidemic activity at 20 mg/kg/day intraperitoneally
in rodents. The 3-phenyl compound afforded the best activity and effectiveness in both normal and hyperlipidemia-induced mice.
The agent lowered lipids by blocking the de novo hepatic synthesis of cholesterol and triglycerides, specifically at the sites
of ATP-dependent citrate lyase, acetyl CoA synthetase,sn-glycerol-3-phosphate acyl transferase and phosphatidylate phosphohydrolase. The agent caused a more rapid clearance of cholesterol
by the fecal route. Cholesterol levels of the chylomicrons, very low density lipoprotein and low density lipoprotein (LDL)
were reduced, whereas high density lipoprotein cholesterol was significantly elevated after drug administration. Triglyceride
content was lowered in the chylomicron and LDL fractions. These modulations of lipid content of serum lipoproteins by the
drug suggest a favorable situation for treatment of hyperlipidemic states. 相似文献
12.
The role of serum lipoproteins as nonantibody-like inhibitors of haemagglutination for rubella virus was investigated. Dissociation
of lipoproteins into their respective lipid and protein components significantly reduced their inhibitory titre. This reduction
was more prominent with the protein component. When mixtures of pure lipids were tested for their haemagglutination inhibitory
activities, no inhibition was observed. Sonication of the three major lipoprotein fractions significantly increased the inhibitory
activities of low density lipoproteins (LDL) and very low density lipoproteins (VLDL) but not high density lipoproteins (HDL).
Succinylation, acetylation, and methylation of the lipoproteins did not appear to affect their inhibitory titre. On the other
hand, phospholipase A treatment significantly increased the inhibitory properties of all lipoproteins fractions. These results
are discussed in terms of the possible mechanisms by which the lipoproteins interact with the rubella haemagglutinins. 相似文献
13.
Rats were fed plant sterols containing campesterol and β-sitosterol in the different proportions, and their distribution in
serum lipoproteins and in liver subcellular fractions was determined. In serum lipoproteins, the percentage as well as the
concentration of plant sterols increased with the increase in the density of lipoproteins. Thus, high density lipoprotein
(HDL) contained the highest and very low density lipoprotein (VLDL), the lowest. Also, there were distinct differences in
the ratio of campesterol to sitosterol among lipoproteins, it was the highest in VLDL and lowest in HDL. Quantitatively, more
than 75% of campesterol and 80% of sitosterol were carried in HDL; the values were significantly different from those of cholesterol
(ca. 70%) in relation to total cholesterol. The distribution of plant sterols in liver subcellular fractions was virtually
the same with that of cholesterol. Both nuclei and microsomes contained approximately 40% of total plant stetols.
A preliminary part of the study was presented at the First Congress of the Federation of Asian and Oceanian Biochemists in
Nagoya, October 1977. 相似文献
14.
Human aortic smooth muscle cells (SMC) specifically bind and take up indiscriminately both the lipid and protein moietics
of homologous25I-very low density lipoproteins (VLDL) and125I-low density lipoproteins LDL). Sixty-five to 80% of absorbed lipids are incorporated into the cell lipids, preferentially
into the phospholipid fraction. Twenty to 35% of the lipid bound and the protein moiety are eliminated from the cells. Half
of the eliminated protein label is recovered as TCA soluble products. Five mM of p-chlorophenoxyisobutyrate (CPIB) raise the
level of intracellular radioactivity derived from the lipid moieties of VLDL and LDL by about 40% via a reduced elimination.
The processing of the protein moiety and lipoprotein binding to the cell surface are not affected by 5.0 mM of CPIB. CPIB
lowers the incorporation of14C-acetate,14C-pyruvate, and32phosphate radioactivity into fatty acids and phospholipids of aortic SMC. Five mM of CPIB reduce the overall palmitic acid
synthesis by shifting from de novo synthesis to the mechanism of chain elongation, although the further elongation to saturated
C18–C24 fatty acids is also depressed. The CPIB-enhanced retention of the lipid-derived lipoprotein radio-activity is interpreted
as a compensatory mechanism providing cellular fatty acids which are deficient as a result of the CPIB inhibited synthetic
processes. 相似文献
15.
Twenty-six patients with clinically confirmed mammary dysplasia and five age-matched controls were treated with α-tocopherol,
600 mg/day. Serum samples collected on the 21st day of the menstrual cycle were analyzed for cholesterol in lipoprotein fractions,
isolated by a combination of precipitation and ultracentrifugation techniques. Eighty-five percent of patients showed objective
and subjective remission from disease following therapy. In mammary dysplasia patients, the ratio of serum cholesterol/high
density lipoprotein cholesterol was higher than those in age-matched controls, an abnormality which was corrected by α-tocopherol
therapy. Furthermore, as a result of therapy, high density lipoproteins increased and ester cholesterol associated with low
density lipoproteins decreased. The results suggest that α-tocopherol may serve as an effective agent in treating patients
with benign breast disease, as well as correct the inherent abnormality in serum cholesterol distribution in mammary dysplasia
patients.
Biochemistry Research Division, Department of Research Medicine. 相似文献
16.
Pe¯teris Alberts Gunnel Klingstrm Vibeke Arrhenius‐Nyberg Catarina Larsson Kjell S. Sakariassen 《European Journal of Lipid Science and Technology》2006,108(6):453-458
The aim of the present study was to assess cholesterol‐containing lipoprotein profiles in minute serum samples. The lipoprotein profiles of KKAy and transgenic KKAy‐CETP mice and of other species were determined. The transgenic KKAy‐CETP mice express the simian enzyme cholesteryl ester transfer protein (CETP). The serum profile of the cholesterol‐containing high‐density (HDL), low‐density (LDL) and very‐low‐density lipoproteins (VLDL) was monitored on a Superose 6 column using fast protein liquid chromatography. Serum from several mouse and rat strains, rabbit, hamster, pig and man was included for comparative and method validation purposes. The chromatograms showed that the transgenic KKAy‐CETP mice had significantly decreased relative levels of HDL vs. VLDL and LDL cholesterol (p <0.001). Introduction of the CETP gene shifted the serum profile of the cholesterol‐containing lipoproteins of the KKAy‐CETP mice closer to the human profile in a dose‐dependent manner, thus making these mice an interesting model for man. The described lipoprotein separation technology offers promising and reliable opportunities for studies of blood lipoprotein profiles with minute serum samples, in both animals and man. 相似文献
17.
Serum cholesterol precursor sterols reflect the activity of cholesterol synthesis. In this study, squalene, methyl sterol
and lathosterol contents were studied in very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density
lipoprotein (HDL) of heterozygous familial hypercholesterolemia patients without and with ileal bypass. The contents of lathosterol
and all methyl sterols (lanosterol, Δ8,24-dimethylsterol, Δ8-dimetylsterol, Δ8-methostenol and methostenol), but not of squalene were increased in all lipoproteins by ileal bypass. The increase in the
free methyl sterols was more marked than that in the esterified ones. The percentage esterification of the methyl sterols
was highest in HDL and lowest in VLDL. Lipoprotein methyl sterol contents were positively correlated with each other and with
cholesterol synthesis. The methyl sterols were slightly concentrated in LDL, and squalene strongly concentrated in VLDL. It
is concluded that long-term stimulation of cholesterol synthesis increases the methyl sterols in all lipoproteins. 相似文献
18.
Fatty acid biosynthesis in Ehrlich cells in vitro was reduced when very low density lipoproteins (VLDL) isolated from the
ascites tumor plasma were added to the incubation medium. The degree of inhibition was dependent on the VLDL concentration.
At the VLDL concentrations usually present in the ascites plasma, there was a 30% decrease in biosynthesis as measured by3H2O incorporation into fatty acids. Analysis of the labeled fatty acids by gas liquid chromatography indicated that this decrease
was due to a reduction in fatty acid de novo biosynthesis and that chain elongation actually was increased when VLDL were
present. Although ascites plasma low- and high density lipoproteins also produced a concentration-dependent inhibition of
fatty acid biosynthesis, their effects were much smaller than those of the VLDL. Studies employing VLDL and radioactive free
fatty acids indicated that the cells took up and utilized fatty acids derived from these lipoproteins. When VLDL were present,
labeled free fatty acid incorporation into cell phospholipids, cholesteryl esters, and CO2 decreased, whereas its incorporation into the cell free fatty acid pool increased. By contrast, the cells incorporated only
very small amounts of fatty acid from either low- or high density lipoproteins. This suggests that the VLDL exert their inhibitory
effect on fatty acid synthesis by supplying exogenous fatty acids to the cells.
Presented in part at the AOCS Spring Meeting, Dallas, April 1975. 相似文献
19.
The effect of protein depletion in the pregnant rat on the polyunsaturated fatty acid incorporation into very low density
lipoproteins (VLDL) has been investigated. The apoprotein pattern of these particles was determined. In in vivo experiments
the amounts of serum and liver triacylglycerol were determined. VLDL were isolated and their apo C concentration calculated.
In in vitro experiments the radioactivity of [3H] leucine incorporated into VLDL apoproteins was measured. The results show that protein depletion during pregnancy promotes
a drastic increase in serum and liver triacylglycerol. The VLDL isolated from these animals show an increase in the triacylglycerol/protein
ratio and a decrease in their content of apo C. Meanwhile, a significant reduction in the [3H]leucine incorporation into apo C peptides by the perfused liver of protein depleted rats was detected. On the other hand,
protein deprivation did not affect labeled linoleic and arachidonic acid incorporation into triacylglycerol of the newly secreted
VLDL. Taking these results together, let us deduce that a defective VLDL is secreted by the liver of the protein depleted
pregnant rats. The abnormal composition of these particles may influence its normal metabolism through their effects on lipoprotein
lipase and this fact could affect the normal supply of polyunsaturated fatty acids to the fetus. 相似文献
20.
The binding of lithocholic acid to different plasma fractions was studied. When whole plasma was incubated for 8 hr, approximately
25% of the incubated [14C]lithocholic acid was bound to the lipoprotein and lipoprotein-free, albumin-rich fractions. An average of 87.6% of the bound-lithocholic
acid was present in the lipoprotein-free, albumin-rich fraction, 7.2% in high density lipoproteins, 2.2% in low density lipoproteins,
1.0% in intermediate density lipoproteins and 2.0% in very low density lipoproteins. Expressed as binding per μg protein,
considerably less [14C]lithocholic acid was bound to the lipoprotein-free, albumin-rich fraction, than to the lipoproteins. The binding of [14C]lithocholic acid after the incubation of the isolated plasma fractions was similar to that found after the incubation of
whole plasma. The highest transfer of [14C]lithocholic acid occurred from the lipoprotein-free, albumin-rich fraction to the lipoprotein fractions. The studies indicate,
that, although the largest amount of lithocholic acid is bound to the lipoprotein-free, albumin-rich fraction, per μg protein,
the binding of lithocholic acid to lipoporteins is more pronounced and stable than that bound to the lipoprotein-free, albumin-rich
fraction. Since lipoproteins, in contrast to albumin, are internalized by most tissues, they may be important carriers into
cells of lithocholic acid and other potentially toxic or tumorigenic bile acids.
Results of this study were presented at the Annual Meeting of the American Society for Clinical Investigation in Washington,
D.C. in May 1988. 相似文献