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1.
Phosphatidylcholine acyltransferase (lecithin:cholesterol acyltransferase or LCAT; EC 2.3.1.43) activity was found to be present
in pig ovarian follicular fluid (POFF), in addition to pig serum (PS). The cholesterol esterification rate in both POFF and
PS is linear with incubation time up to 2 hr. The mean absolute rate of POFF-cholesterol esterification was 8.1±0.4 nmoles
per ml per hr approximately one-fourth of that in PS. However, the fractional rate (percent of labeled cholesterol esterified
per hr) of POFF-cholesterol esterification was similar to that observed in PS. There was little variation of absolute rate
of cholesterol esterification in the fluid obtained from different sizes of follicles. Fatty acid or triacylglycerol did not
participate in the reaction of cholesterol esterification in POFF. No appreciable change in enzymatic activity was found from
storing POFF at 4 C for periods of time up to 24 hr or at −70 C up to 2 months, but activity was lost thereafter. On the other
hand, PS showed a much longer period of stability (5 days at 4 C and 9 months at −70 C). A discrepancy between the fatty acid
composition of cholesteryl esters formed by the LCAT reaction and the fatty acid composition at the C-2 position of phosphatidylcholine
led us to propose a two-step mechanism for the LCAT reaction. It is concluded that the LCAT of POFF, as well as that of plasma,
is specific for individual fatty acids rather than for the fatty acid composition of phosphatidylcholine. The fatty acid concentration
of lysophosphatidylcholine decreased during prolonged incubation times (6 to 21 hr) suggesting that the increased lysophosphatidylcholine
formed as a product of the LCAT reaction may be reused as substrate for the LCAT reaction or for hydrolysis by lysophosphatidylcholine
hydrolase.
Presented at the AOCS Meeting, New York, May 1977. 相似文献
2.
Cholesterol esterification was studied in adult and cord serum by measureing the initial rate of lecithin-cholesterol acyl
transferase (LCAT) activity. Cord serum had about one-third as much free and esterified cholesterol and about one-half as
much LCAT as adult serum. When the adult LCAT activities are plotted against the individual's serum free cholesterol levels
a straight line relationship results (0.101±.005% cholesterol esterified per min). Cord serum LCAT activities (.135±.0407%
cholesterol esterified per min) in the main fall above the adult line. Our results show that cord serum can esterify cholesterol
at a rate equal to or higher than adult serum when the LCAT activity is related to the amount of serum free cholesterol present. 相似文献
3.
In our previous studies, we found that circulating thyroid hormone levels alter cholesterol partition between plasma and erythrocytes
by changing the phospholipid content of erythrocytes (Ruggiero, F.M.,et al. (1984)Horm. Metabol. Res. 16, 37–40; Ruggiero, F.M.,et al. (1987)Lipids 22, 148–151). As an extension of this work, we now followed the exchange of free cholesterol between plasma and erythrocytes
in control, hyperthyroid and hypothyroid rats under various experimental conditionsin vitro. In control rats, erythrocytes incubated with plasma at 37°C for 4 hr lose 10% of cholesterol which was esterified by lecithin:
cholesterol acyltransferase (LCAT) present in the plasma. In hyperthyroid rats, erythrocytes incubated with plasma lose 30%
of cholesterol within the same time. By contrast, in the case of hypothyroid rats incubation for 4 hr was necessary to transfer
24% of free cholesterol from plasma to erythrocytes. Inhibition of cholesterol esterification did not affect the loss of erythrocyte
cholesterol in control and in hyperthyroid rats. Ca2+ increased the LCAT activity in the plasma of these rats. The findings shed light on the role of thyroid hormones in regulating
cholesterol levels in plama through active cholesterol transfer between plasma and erythrocytes. 相似文献
4.
An important factor which determines the movement of cholesterol in and out of the cells is the free cholesterol (FC)/esterified
cholesterol (EC) ratio in the plasma. Although this ratio has been shown to be increased in several types of malignancies
in humans as well as experimental animals, it is not known whether such an abnormality is found in breast cancer patients.
Furthermore, the reasons for such an increase in cancer patients are unknown. We studied the plasma lipid composition and
the activity of lecithin-cholesterol acyltransferase (LCAT), the enzyme responsible for the formation of most of EC in human
plasma, in 12 women with breast cancer and 9 agematched control women. The plasma EC concentration was found to be significantly
decreased in cancer patients, whereas the FC concentration was unchanged, leading to increased FC/EC ratios (P<0.05). The concentration of phosphatidylcholine, the acyl donor in the LCAT reaction, was decreased significantly, whereas
all other phospholipids were unaffected. The cholesterol-esterifying activity of LCAT was significantly lower in cancer patients,
whether assayed with endogenous substrates (P<0.05), or with an exogenous substrate (P<0.01). However, another function of the enzyme, namely the lysolecithin acyltransferase activity, was increased (P<0.02), indicating that the enzyme concentration in plasma may not be decreased. These results show that the increase in the
FC/EC ratio in cancer patients is due to an impaired esterification of cholesterol by plasma LCAT, probably due to an alteration
in the composition of substrate lipoproteins, or the presence of an inhibitory factor. 相似文献
5.
Native fish-eye disease plasma, which is deficient of both high density lipoproteins (HDL) and lecithin-cholesterol acyltransferase
activity (α-LCAT), processing the free cholesterol of these lipoproteins, has been supplemented with normal isolated HDL2 or HDL3 and incubated in vitro at 37 C. After incubation for 0,7.5 and 24 hr the very low density (VLDL) and low density (LDL) lipoproteins
as well as HDL were isolated, and their contents of triglycerides, phospholipids and free, esterified and total cholesterol
were quantified. The resulting net mass transfer of the different lipids revealed a functioning transfer of cholesteryl esters
and all other analyzed lipids between the lipoproteins, although no de novo esterification of the HDL cholesterol by LCAT
in this plasma occurred. In accordance with previous findings there was a functioning esterification process of the free cholesterol
of the combined VLDL and LDL of fish-eye disease plasma. The present results make it reasonable to conclude that the lack
of HDL cholesterol esterification in this disease is not a result of a deficiency of cholesteryl ester transfer or lipid transfer
activities. 相似文献
6.
Chlorpromazine (CPZ), a major tranquilizer, was found to be a potent inhibitor of lecithin:cholesterol acyltransferase (LCAT,
EC 2.3.1.43) in the plasma of normal man, rat, rabbit and dog in vitro. The inhibitory effect of CPZ reached 35–50% at 0.5
mM depending on species; dog plasma LCAT appeared to be somewhat more sensitive than that of the other species. In rats fed
CPZ or lidocaine for 14 days (0.05% in the diet), there was no statistically significant change in total plasma cholesterol
levels or the size of the plasma-free (unesterified) cholesterol pool. However, 5 hr after an intracardial injection of [14C] cholesterol, the percentage of plasma [14C] cholesterol that was esterified was significantly lower (ca. 6%, p<0.05) in the CPZ-treated group, suggesting that CPZ
may also inhibit LCAT to some extent in vivo. The percentage of plasma [14C] cholesterol esterified in the lidocainetreated group was similar to control values and did not reflect its ability to inhibit
LCAT in vitro. 相似文献
7.
Serum and hepatic cholesterol content in rats treated with polychlorinated biphenyls (PCBs, KC-400) were increased compared
to those of control rats. This increase of cholesterol content was reduced to control level by simultaneous administration
of ethyl p-chlorophenoxyisobutyrate (CPIB). Also, when lecithin-cholesterol acyltransferase (LCAT) (EC. 2.3.1.43) activity
was expressed as the net cholesterol esterification, the acyltransferase activity in rats treated with PCBs was elevated,
while the elevated acyltransferase activity was brought to control level by simultaneous administration of CPIB. On the other
hand, the amount of bile of rats treated with CPIB, PCBs and PCBs-CPIB was increased, but free and total cholesterol content
in bile of these treated rats was decreased to 40–60% of those of control rats. Moreover, cytochrome P-450 content in liver
microsomes of rats treated with CPIB, PCBs and PCBs-CPIB was increased. At the same time, cholesterol-metabolizing activity
in liver microsomes of rats treated with CPIB, PCBs and PCBs-CPIB also was elevated. Similar results were obtained for drug
metabolizing (aniline hydroxylation and aminopyrine N-demethylation) activity. In addition, the amount of bile acids excreted
from rats treated with CPIB, PCBs and PCBs-CPIB was increased compared to that of control rats.
These results suggest that hypercholesterolemia induced by oral ingestion of PCBs is recovered by CPIB treatment and that
this hypocholesterolemic effect of CPIB may be related partly to the elevation of hepatic mixed function oxidase activity
for cholesterol catabolism. 相似文献
8.
Marc J. Van Rafelghem John P. Vanden Heuvel Lawrence A. Menahan Richard E. Peterson 《Lipids》1988,23(7):671-678
Alterations in lipid metabolism were axamined in adult male Sprague-Dawley rats seven days after a single intraperitoneal
injection of perfluorodecanoic acid (PFDA; 20, 40 or 80 mg/kg). Because PFDA treatment caused a dose-related reduction in
feed intake, the response of vehicle-treated rats pair-fed to those receiving PFDA was monitored to distinguish direct effects
of the perfluorinated fatty acid from those secondary to hypophagia. Carcass content of lipid phosphorus and free cholesterol
decreased in dose-dependent fashion in both PFDA-treated and pair-fed rats. Carcass triacylglycerols diminished in a similar
manner, yet PFDA-treated rats at each dose had a higher concentration of neutral acylglycerols than their vehicle-treated,
pair-fed counterparts. In vehicle-treated, pair-fed rats at the 80 mg/kg dose level, lipid phosphorus and free cholesterol
as a proportion of carcass fat increased, whereas the share of the triacyl-glycerols declined. Because of the higher concentration
of triacylglycerols in the carcass of rats treated with 80 mg/kg PFDA, enrichment of lipid phosphorus and free cholesterol
in carcass fat was less than in their pair-fed partners. The amount of lipid phosphorus and free cholesterol per hepatocyte
was similar in both PFDA-treated rats and their pair-fed partners. Liver triacyl-glycerols were markedly increased in PFDA-treated
rats. A similar but less extensive augmentary effect of PFDA on hepatic esterified cholesterol was found. Concentration of
triacylglycerols in plasma was not elevated in PFDA-treated rats, in spite of hepatic accumulation of esterified compounds.
Also, the plasma level of free fatty acids and 3-hydroxybutyrate was similar in all treatment groups, including those receiving
PFDA. Thus, the administration of PFDA appears to divert fatty acids from oxidation toward esterification in the liver. 相似文献
9.
Cupric ions were administered subcutaneously to male Sprague-Dawley rats at a single dose of 200 μmol/kg. At 24 hr after administration,
a remarkable increase of total and free cholesterol was seen in the rat serum. Also, when lecithin-cholesterol acyltransferase
(LCAT) (E.C. 2.3.1.43) activity was expressed as the percentage of the total serum that free cholesterol esterified, the acyltransferase
activity in rats treated with cupric ions showed a slight decrease while the triglyceride content in rat serum and liver decreased
by 54% and 61%, respectively. However, the content of hepatic cholesterol in rats treated with cupric ions did not show such
a marked change.
On the other hand, acid cholesteryl ester hydrolase activity (Acid CEH) (E.C. 3.1.1.14) in liver lysosomes of rats treated
with cupric ions showed a marked decrease with increasing cupric ion concentration both in vivo and in vitro. Furthermore,
cupric ions caused a marked release of the lysosomal enzymes cathepsin D and β-glucuronidase into the cytosolic fraction.
The changes in acid cholesteryl ester hydrolase activity induced by cupric ions appear to be a direct effect of cupric ions
on the enzyme. These results suggest that excessive cupric ion concentrations could cause various disorders in lipid metabolism. 相似文献
10.
Hepatic and serum phytosterol concentrations were compared in the rat under basal conditions and during activated cholesterol
and bile acid production due to squalene and cholestyramine feeding. Both treatments consistently decreased hepatic and serum
levels of sitosterol and campesterol and, unlike esterified cholesterol, esterified plant sterols were not increased in liver
during squalene feeding. Serum levels of phytosterols were decreased quite proportionately to those in the liver. The hepatic
levels of sitosterol and campesterol closely correlated with each other, but not with cholesterol levels. The percentage esterification
of both phytosterols was lower than that of cholesterol. The results indicate that activation of hepatic sterol production
leads to depletion of hepatic plant sterols. It is suggested that poor esterification of plant sterols may contribute to this
decrease. 相似文献
11.
The relationship between LCAT mediated HDL modification and the redistribution of lipoprotein-unassociated apoA-IV to HDL
was investigatedin vitro. Immunoaffinity-isolated rat lipoprotein-unassociated apoA-IV was added to apoB-, apoE-, apoA-IV depleted, [3H]cholesterol labelled rat plasma and incubated at 37°C. The addition of lipoprotein-unassociated apoA-IV resulted in a modest
(10%) but significant reduction in the rate of cholesterol esterification. Incubations conducted in the presence of active
LCAT led to a time-dependent increase in the amount of the3H label retained by an anti-apoA-IV immunoaffinity column. Lipoproteins retained by the anti-apoA-IV immunoaffinity column
had experienced a greater conversion of [3H]cholesterol to [3H]cholesteryl esters (48% esterification at 30 min) than the unretained lipoproteins (19% esterification at 30 min). These
data suggest that during the course of LACT-induced cholesterol esterification, lipoprotein-unassociated apoA-IV transfers
to a subpopulation of HDL which has been modified by LCAT to a greater extent than the remaining HDL. Further analysis of
the data demonstrates that 48% cholesterol esterification is sufficient to allow apoA-IV to be accommodated on the surface
of an HDL particle. 相似文献
12.
Tchoua U Rosales C Tang D Gillard BK Vaughan A Lin HY Courtney HS Pownall HJ 《Lipids》2010,45(12):1117-1126
Serum opacity factor (SOF) is a streptococcal protein that disrupts the structure of human high density lipoproteins (HDL)
releasing lipid-free apo A-I while forming a large cholesteryl ester-rich particle and a small neo HDL. Given its low cholesterol
and high phospholipid contents, we tested the hypotheses that neo HDL is a better substrate for cholesterol esterification
via lecithin:cholesterol acyltransferase (LCAT), better than HDL as an acceptor of THP-1 macrophage cholesterol efflux, and
improves reduction of oxidized LDL-induced production of inflammatory markers. We observed that both cholesterol efflux and
esterification were improved by recombinant (r)SOF treatment of whole plasma and that the underlying cause of the improved
cholesterol esterification in plasma and macrophage cholesterol efflux to rSOF-treated plasma was due to the rSOF-mediated
conversion of HDL to neo HDL. Moreover, the reduction of secretion of TNF-α and IL-6 by THP-1 cells by neo HDL was twice that
of HDL. Studies in BHK cells overexpressing cholesterol transporters showed that efflux to neo HDL occurred primarily via
ABCA1 not ABCG1. Thus, rSOF improves two steps in reverse cholesterol transport with a concomitant reduction in the release
of macrophage markers of inflammation. We conclude that rSOF catalyzes a novel reaction that might be developed as a new therapy
that prevents or reverses atherosclerosis via improved reverse cholesterol transport. 相似文献
13.
Effects of ketoconazole on cholesterol synthesis and precursor concentrations in the rat liver 总被引:1,自引:0,他引:1
Ketoconazole, an antimycotic agent, given to rats for a week as 0.05% food addition had no effect on the hepatic concentrations
of free and esterified cholesterol or on the activity of acyl coenzyme A: cholesterol-acyltransferase (ACAT). However, the
levels of free methylated cholesterol precursors, especially lanosterols, less markedly Δ8,24 and Δ8-dimethyl sterols and monomethyl sterols, were increased after only one day's treatment, while those of esterified methyl
sterols were increased inconsistently, and those of free and esterified Δ8-lathosterol, lathosterol and desmosterol were not affected at all. Cholestyramine treatment had no significant effect on
ACAT in spite of a decrease in the hepatic content of esterified cholesterol and caused a marked increase in the free cholesterol
precursor levels, especially in those of lathosterols. Cholestyramine given to ketoconazole-treated rats increased the hepatic
levels of Δ8 and Δ7-lathosterols but not desmosterol or methylated cholesterol precursors. Ketoconazole increased and cholestyramine markedly
decreased plantssterols, sitosterol and campesterol in the liver. In serum, the contents of both lanosterols and lathosterol
were increased but that of cholesterol tended to be decreased by ketoconazole (−19%). The results indicate that ketoconazole
impairs demethylation processes at C-14 and to some extent at C-4 in the rat liver, resulting in lowered serum cholesterol
level. 相似文献
14.
The relationship between lecithin:cholesterol acyltransferase (LCAT) activity and weight loss in dogs was investigated. Four
experimental weight-loss diets were fed to 12 obese female beagles for 56 days in a partial crossover design (n = 6). High- (HGI) or low- (LGI) glycemic index starch and diacylglycerol or triacylglycerol oils were combined to compose
experimental diets with similar fatty acid profiles. Food intake and body weights were measured daily and weekly, respectively.
Fasted blood samples were drawn at day 0, day 28, and day 56 to measure plasma LCAT activity and total (TC), unesterified
(UC), and esterified (EC) cholesterol concentrations, and for fatty acid analysis of the phospholipid (PL) and EC fractions.
The LGI groups lost more weight than the HGI groups due to starch digestibility differences. An HGI starch effect on TC and
UC concentrations was observed but was unrelated to weight loss. LCAT activities increased over time but were not different
after controlling for percentage weight loss. However, a positive linear correlation was found between LCAT and UC concentrations
in all groups. Plasma PL fatty acid profiles reflected the diets fed, but increases in 16 and 18 carbon saturated and monounsaturated
fatty acids in all groups appeared to be an effect of fatty acid mobilization from storage sites. Both plasma PL and EC fatty
acid profiles were similar with both acylglycerol types and EC fatty acids reflected linoleic acid specificity with minimal
diet or time effects. 相似文献
15.
Plasma from a patient with fish eye disease has been enriched with autologous high density lipoproteins (HDL) and supplemented
with highly purified normal human plasma lecithin:cholesterol acyltransferase (LCAT). Incubation of such plasma at 37 C in
vitro resulted in normalization of its low HDL cholesteryl ester percentage, from 23% to 79%, associated with a two-fold increase
in both the cholesteryl ester and triglyceride contents of the HDL fraction, as compared to incubation experiments with absent
or heat-inactivated purified normal LCAT.
The normalization of the HDL cholesteryl ester percentage induced by incubation with purified normal LCAT also was accompanied
by an increase in the size of the original fish eye disease HDL particles, which had a mean mass of 115 kd, to HDL particle
populations with mean particle masses ranging from 130–220 kd, depending on the concentration of purified LCAT in the incubate.
Both HDL cholesterol esterification and particle enlargement were abolished completely by the LCAT inhibitor DTNB and by heat
inactivation of the purified normal LCAT. The results give further evidence that fish eye disease is an α-LCAT deficiency. 相似文献
16.
Hypolipidemic effects of clofibrate and selected chroman analogs in fasted rats: I. Chow-fed animals
M. O'Brien S. T. Patel A. Mukhopadhyay H. A. I. Newman D. R. Feller S. S. Kokrady D. T. Witiak R. R. Lanese J. C. Rice 《Lipids》1981,16(12):903-911
The hypolipidemic properties of ethyl 6-chlorochroman-2-carboxylate (II), ethyl 6-phenylchroman-2-carboxylate (III) and ethyl
6-cyclohexylchroman-2-carboxylate (IV) were compared to clofibrate (I) in fasted normolipidemic rats. The chroman analog II,
like its parent compound, clofibrate, reduced serum and α-lipoprotein cholesterol concentrations. Although analog III had
no effect on serum cholesterol, it caused a slight elevation of α-lipoprotein cholesterol concentration. Serum free cholesterol
was increased and LCAT activity was reduced in clofibrate-treated rats. The hypolipidemic agents had no consistent effect
on liver lipid concentrations and liver microsomal HMG-CoA reductase activity. In addition, we have shown that drug efficacies
varied directly with seasonal variations in serum lipid concentrations. 相似文献
17.
Previous investigations had demonstrated that Fu5AH rat hepatoma cells accumulated large quantities of esterified cholesterol
when grown in hyperlipemic rabbit serum. The present investigation has determined the sources of the cellular esterified cholesterol
when the cells were grown in hyperlipemic serum. Cellular esterification of endogenous and exogenous free cholesterol contributed
10% and 30%, respectively. The remaining 60% of the accumulated cellular esterified cholesterol was derived from exogenous
(serum) cholesteryl esters. Evidence for the hydrolysis of a portion of the incorporated esterified cholesterol is presented.
A stimulation of free cholesterol incorporation and cellular esterification is elicited by hyperlipemic serum and serum lipoproteins
when compared to normolipemic serum present at equivalent exogenous cholesterol concentrations. The effect of hyperlipemic
serum is reduced by Tween-80 and Triton WR-1339. Comparative data on esterified cholesterol accumulation, free cholesterol
incorporation, and cellular cholesterol esterification in Fu5-5 rat hepatoma cells, L-cells, and rabbit aortic medial cells
are presented.
This work was done during the tenure as Established Investigator of the American Heart Association. 相似文献
18.
The properties and fatty acid and sterol specificity of cholesterol-esterifying enzyme (EC 3.1.1.13) in rat brain were studied.
The enzyme utilized free fatty acid for esterification, and activity was maximal at pH 5.6. Exogenous ATP and CoA did not
stimulate the incorporation of free fatty acids into sterol esters. Substrates dispersed in Tween 20 or Triton X-100 were
just as effective as the substrates dissolved in acetone solution, while dispersion in propylene glycol or sodium taurocholate
was not as effective. Snake venom phospholipase A2 (EC 3.1.1.4) increased the esterification of cholesterol in the absence of added fatty acid. The fatty acid specificity data
indicated that oleic and palmitic acids were the preferred fatty acids. Little or no esterification occurred in the presence
of long chain fatty acids (C20–C24). Esterification of cholesterol with palmitate or stearate was not affected by the presence of oleic acid in the mixture.
Thus, the nonrequirement of the brain-esterifying enzyme for a bile acid or for an amphiphile such as an unsaturated fatty
acid suggests that micellar solubilization of the substrate is not essential for activity. Although the brain enzyme catalyzed
the esterification of desmosterol, cholesterol was the preferred substrate. Neither lanosterol (C29 sterols) nor Δ7-dehydrocholesterol was esterified to any significant extent. The presence of low concentrations of desmosterol
increased cholesterol esterification slightly, while there was a concentration-dependent inhibition of demosterol esterification
by cholesterol. These data on fatty acid and sterol specificity of the esterifying enzyme correlate well with the composition
of sterol esters present in developing rat brain. 相似文献
19.
The effects of aging on the hepatic metabolism of cholesterol were studied in 1-, 6- and 24-month-old male Sprague-Dawley
rats. Microsomal 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity, which regulates cholesterol biosynthesis,
decreased from 835±144 (SEM) pmol/min/mg protein in the youngest group to 219±34 and 205±53 pmol/min/mg protein (p<0.001)
in the 6- and 24-month-old groups, respectively. Cholesterol 7α-hydroxylase activity, which governs bile acid synthesis, was
gradually reduced from 70±14 pmol/min/mg protein in the 1-month-old group to 32±7 and 16±3 pmol/min/mg protein (p<0.05) in
the 6- and 24-month-old groups, respectively. Acyl coenzyme A:cholesterol acyltransferase activity, which catalyzes the esterification
of cholesterol, averaged 431±47 and 452 ±48 pmol/min/mg protein in the 1- and 6-month-old groups, respectively, and was increased
to 585±55 pmol/min/mg protein (p<0.05) in the 24-month-old group. The level of total cholesterol showed an age-related increase
from 1.56±0.16 mg/g liver in the 1-month-old group to 1.70±0.15 and 2.20±0.19 mg/g liver (p<0.05) in the 6- and 24-month-old
groups, respectively. The increase was mainly caused by an accumulation of esterified cholesterol. We conclude that a marked
decrease in HMG-CoA reductase occurs between 1 and 6 months of age; thereafter the enzyme activity stays unchanged. The activity
of cholesterol 7α-hydroxylase decreases progressively and drastically with age, whereas the capacity for esterifying cholesterol
increases slightly. We speculate that the reduced conversion of cholesterol to bile acids may be one explanation of the age-related
increase of plasma cholesterol seen in rats. 相似文献
20.
M. Nishikawa K. Seki Y. Matsuzawa Y. Minami S. Kawata S. Miyoshi Y. Imai R. Saitoh S. Noda S. Tamura S. Tarui 《Lipids》1984,19(10):777-783
The mechanism by which high doses of estrogen influences lipid metabolism was studied with a microtubular blocking agent.
Castrated male rats received oral injection daily for 14 days of 3 mg hexestrol in olive oil, or oil alone as controls. About
half of the animals in each group were injected intraperitoneally with 4 mg/100 g body weight colchicine 3 hr before they
were killed. Hexestrol treatment caused an accumulation of esterified cholesterol in the liver while it decreased those in
serum. Triglyceride concentrations slightly decreased in the liver but were unaffected in serum. On polyacrylamide-gel disc
electrophoresis, the peaks of high density lipoproteins (HDL) and low density lipoproteins (LDL) were decreased remarkably.
Electron microsopic examination of hepatocytes revealed electron-lucent lipid droplets in the cytoplasm.
After a colchicine treatment of the control animals, concentrations of esterified cholesterol and triglycerides markedly increased
in the liver, while those in serum decreased. Electron microscopic examination of hepatocytes revealed numerous secretory
vesicles filled with nascent VLDL. In hexestrol-treated animals, the colchicine treatment was associated with marked decreases
in serumesterified cholesterol and triglyceride as seen in the controls. However, there were no further increases of esterified
cholesterol in the liver, and the increase of triglycerides was slight. Electron microscopic examination showed less secretory
droplets than in the controls.
These data suggest that very low density lipoproteins (VLDL) synthesis in the liver of hexestrol treated rats was inhibited.
An accumulation of esterified cholesterol with a marked decrease in serum could not be accounted for by the inhibition of
lipoproteins secretion, but rather by their enhanced entry into the liver. 相似文献