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1.
Sphingomyelin metabolism is a novel signal transduction pathway related to cell differentiation, proliferation, and apoptosis.
Alkaline sphingomyelinase (alk-SMase) is specifically present in the intestinal tract of many species. The enzyme is important
in digestion of dietary sphingomyelin. Milk is the ony exogenous source of sphingomyelin for an infant, and digestion of milk
sphingomyelin may be important for development of intestinal mucosa. It is unknown whether alk-SMase is present before birth
and whether it changes after birth and during the suckling period. We studied activities, expression, and distribution of
alk-SMase in rat fetus and newborn. The changes of acid and neutral SMase as well as alkaline phosphatase were analyzed for
comparison. Little activity of alk-SMase was identified up to gestation day 20, but increased 10 times during the following
2 d. After birth, the activity continused to increase during the following 4 wk. Western blot using IgY antibody against rat
alk-SMase failed to identify the enzyme at gestation day 20 but clearly showed the protein at day 22. The distribution pattern
of the enzyme along the intestinal tract in fetus was largely the same as in adult animals, but became more pronounced after
birth. Short-term weaning had no effect on alk-SMase activity. The activities of acid and neutral SMase were high at gestation
day 20 and decreased significantly before birth. The changes of alk-SMase also differed from those of alkaline phosphatase,
another brush border enzyme. Thus, we conclude that alk-SMase is rapidly expressed during the last days of gestation and that
the newborn rat acquires the ability to digest milk sphingomyelin early in life. 相似文献
2.
To address the role of cell membrane neutral sphingomyelinase (EC 3.1.4.12; SMase) in the regulation of cholesterol metabolism
in the liver parenchymal cell, we examined the effect of exogenous neutral SMase on the metabolism of cholesteryl esters and
the secretion of VLDL and biliary lipids in isolated rat hepatocytes. We show that treatment of hepatocytes with SMase (20
mU/mL) resulted in the intracellular buildup of cholesteryl esters, increased ACAT (EC 2.3.1.26) activity without affecting
the ACAT2 mRNA level, and increased cytosolic and microsomal cholesteryl ester hydrolase (EC 3.1.1.13) activity. This was
accompanied by increases in the secretion of biliary. bile acid, phospholipid, and cholesterol and in increased cholesterol
7α-hydroxylase (EC 1.14.13.17) activity and levels of mRNA, as well as decreased levels of apoB mRNA and a decreased secretion
of VLDL apoB (apoB-48, ∼45%; apoB-100, ∼32%) and lipids (∼55%). Moreover, the VLDL particles secreted had an abnormal size
and lipid composition; they were larger than controls, were relatively enriched in cholesteryl ester, and depleted in TG and
cholesterol. Cell-permeable ceramides did not replicate any of the reported effects. These findings demonstrate that the increased
cholesteryl ester turnover, oversecretion of biliary cholesterol and bile acids, and undersecretion of VLDL cholesterol and
particles are concerted responses of the primary hepatocytes to exogenous neutral SMase brought about by regulation at several
levels. We suggest that plasma membrane neutral SMase may have a specific, ceramide-independent effect in the regulation of
cholesterol out-put pathways in hepatocytes. 相似文献
3.
Incubation of Caco-2 cells, a human intestinal cell line, with 25-hydroxycholesterol (25-HOC) markedly enhanced cellular cholesteryl
ester formation determined by incorporation of [14C]oleic acid into intracellular cholesteryl [14C]oleate. The stimulation by 25-HOC of cholesteryl ester formation was suppressed by staurosporine, a kinase inhibitor, but
not by cycloheximide or actinomycin D. The specific activity of microsomal acyl-coenzyme A:cholesterol acyltransferase (ACAT)
increased two-fold in cells treated with 10 μM 25-HOC for 5 h. ACAT activity decreased when microsomes were incubated without
sodium fluoride, a phosphatase inhibitor, but the decrease in ACAT activity in cells stimulated with 25-HOC was more pronounced.
The results suggest that protein phosphorylation may be involved in the stimulation of cholesteryl ester formation by 25-HOC
in Caco-2 cells. 相似文献
4.
5.
Marie-Laure Favier Pierre-Etienne Bost Christian Demigné Christian Rémésy 《Lipids》1998,33(8):765-771
A viscous hydrocolloid (guar gum, GG; 2.5% of the diet) or a steroid sequestrant (cholestyramine; 0.5% of the diet) was included
in semipurified diets containing 0.2% cholesterol to compare the cholesterol-lowering effects of each agent in rats. In the
present model, GG significantly lowered plasma cholesterol (−25%), especially in the density <1.040 kg/L fraction, whereas
cholestyramine was less potent. Bile acid fecal excretion significantly increased only in rats fed cholestyramine, similar
to the cecal bile acid pool; the biliary bile acid secretion was accelerated by GG, but not their fecal excretion, whereas
GG effectively enhanced neutral sterol excretion. As a result, the total steroid balance (+13 μmol/d in the control) was shifted
toward negative values in rats fed the GG or cholestyramine diets (−27 or −50 μmol/d, respectively). Both agents induced liver
3-hydroxy-3-methylglutaryl-CoA reductase, but cholestyramine was more potent than GG in this respect. The present data suggest
that, at a relative low dose in the diet, GG may be more effective than cholestyramine in lowering plasma cholesterol by impairing
cholesterol absorption and by accelerating the small intestine/liver cycling of bile acids, which is interestingly, accompanied
by reduction of bile acid concentration in the large intestine. 相似文献
6.
Sarojini J. K. A. Ubhayasekera Alba Tres Rafael Codony Paresh C. Dutta 《Journal of the American Oil Chemists' Society》2010,87(2):173-184
Chicken is the most widely consumed meat all over the world due to chickens being easy to rear, their fast growth rate and
the meat having good nutritional characteristics. The main objective of this paper was to study the effects of dietary fatty
by-products in low, medium and high levels of oxidized lipids and trans fatty acids (TFAs) on the contents of cholesterol and oxycholesterols in meat, liver, and plasma of chickens. A palm fatty
acid distillate, before and after hydrogenation, and a sunflower–olive oil blend (70/30, v/v) before and after use in a commercial
frying process were used in feeding trials after adding 6% of the fats to the feeds. Highly oxidized lipid and TFA feeds significantly
increased the contents of cholesterol and oxycholesterols in all tissues of chicken (0.01 < p ≤ 0.05). The contents of oxycholesterols in chicken meat, liver and plasma obtained from TFA feeding trials varied between
17 and 48 μg/100 g in meat, 19–42 μg/100 g in liver and 105–126 μg/dL in plasma. In contrast, in the oxidized lipid feeding
trials, oxycholesterols varied between 13 and 75 μg/100 g in meat, 30–58 μg/100 g in liver and 66–209 μg/dL in plasma. Meat
from chickens fed with feeds containing high levels of TFAs or oxidized lipids may contribute to higher ingestion of cholesterol
and oxycholesterols by humans. 相似文献
7.
Furan fatty acids (furan-FA) can be formed by auto-oxidation of conjugated linoleic acids (CLA) and may therefore be ingested
when CLA-containing foodstuff is consumed. Due to the presence of a furan ring structure, furan-FA may have toxic properties,
however, these substances are toxicologically not well characterized so far. Here we show that 9,11-furan-FA, the oxidation
product of the major CLA isomer cis-9,trans-11-CLA (c9,t11-CLA), is not toxic to human intestinal Caco-2 cells up to a level of 100 μM. Oil-Red-O staining indicated
that 9,11-furan-FA as well as c9,t11-CLA and linoleic acid are taken up by the cells and stored in the form of triglycerides
in lipid droplets. Chemical analysis of total cellular lipids revealed that 9,11-furan-FA is partially elongated probably
by the enzymatic activity of cellular fatty acid elongases whereas c9,t11-CLA is partially converted to other isomers such
as c9,c11-CLA or t9,t11-CLA. In the case of 9,11-furan-FA, there is no indication for any modification or activation of the
furan ring system. From these results, we conclude that 9,11-furan-FA has no properties of toxicological relevance at least
for Caco-2 cells which serve as a model for enterocytes of the human small intestine. 相似文献
8.
Dietary sphingomyelin (SM) may have regulatory effects on cell proliferation and tumorigenesis in the colon. Alkaline sphingomyelinase
(SMase) is the major enzyme responsible for hydrolysis of SM in the gut. Previously we purified the enzyme and showed that
the presence of glycerophospholipids inhibited SM hydrolysis induced by alkaline SMase in vitro. In the present work, we studied the effects of TG, DG, FA, ceramide, and cholesterol on SM hydrolysis catalyzed by purified
alkaline SMase. The results showed that both TG (triolein and tristearin) and DG (1,2-dioleoyl-sn-glycerol and 1,2-distearoyl-rac-glycerol) inhibited the activity of alkaline SMase. 1-Mono-oleoyl-rac-glycerol, 1-monostearoyl-rac-glycerol, stearic acid, oleic acid, linoleic acid, linolenic acid, and arachidonic acid stimulated the activity of alkaline
SMase at 0.4–0.8 mM concentrations but inhibited the enzyme at higher concentrations. There was no difference between the
effects induced by saturated and unsaturated FA. A short-chain FA such as lauric acid had a stronger stimulatory effect at
low concentrations and weaker inhibitory effect at high concentrations than long-chain FA. Choosing linoleic acid as an example,
we found that FA had similar effects on both alkaline SMase and neutral SMase. Cholesterol and ceramide when mixed with FA
to increase its solubility in bile salt micelles inhibited SMase activity. In conclusion, glycerides, FA, ceramide, and cholesterol
influence SM hydrolysis catalyzed by intestinal alkaline SMase. The presence of lipids in the diet may thus influence the
course of SM digestion in the gut and thereby the exposure of colon to SM metabolites. 相似文献
9.
Some tetracycline (TC) antibiotics, including TC and anhydrotetracycline, have been found to enhance specific binding of low
density lipoprotein (LDL) to both LDL receptor-positive and-negative cells at relatively higher concentrations. When incubated
at 37°C, the ability of LDL receptor-negative human fibroblasts to bind 125I-LDL was increased from<2 to 45 ng/mg by 170 μM TC. In normal human fibroblasts and Hep G2 cells, 125I-LDL binding was elevated 1.4- to 2-fold by 113 μM TC. The 125I-LDL binding in the presence of TC was diminished by both heparin and EDTA. The enhancement by TC was not observed when 125I-LDL binding was assayed at 4°C. TC enhanced LDL binding to paraformaldehyde-fixed Hep G2 cells, excluding LDL receptor induction
in the mechanism. These results demonstrated that TC enhanced cellular LDL binding through a process not involving functional
LDL receptors. 相似文献
10.
Manuela Machado Luís M. Rodriguez-Alcalá Manuela Pintado Ana Maria Gomes 《European Journal of Lipid Science and Technology》2023,125(10):2300037
The purpose of this work was to evaluate coconut oil's effect on lipid metabolism-related diseases and immune response using in vitro models. The coconut oil doses were selected according to the results of the safety evaluation performed through genotoxicity and cytotoxicity tests. Then its capacity to modulate obesity-related metabolism was evaluated by measuring adipolysis in 3T3-L1 differentiated adipocytes and hepatic lipid accumulation in hepatocytes (Hep G2). The immunomodulatory activity was evaluated using Caco-2 cells and quantifying pro-inflammatory cytokines’ production (IL-6, IL-8, and TNF-α). Coconut oil, mainly comprised of medium-chain fatty acids (>60% of total fatty acids), showed a high antioxidant capacity (125.76 ± 11.63 µM trolox equivalent/mL). The results showed that coconut oil was capable of reducing 68% of the lipid accumulation in hepatocytes and 42% in adipocytes. It was also capable of modulating the immune response in IL-1β Caco-2 stimulated cells, reducing IL-6 secretion (22% in the presence of 10 mg/mL of coconut oil and by 19% when 15 mg/mL) and TNF-α secretion (90% and 42% in the presence of 15 or 10 mg/mL of coconut oil, respectively). In short, coconut oil shows great potential for the development of functional foods and nutraceuticals targeting lipid metabolism-related diseases. Practical applications: This study describes the impact of organic virgin coconut oil on obesity-related metabolism and immune response. Despite the high content of saturated fatty acids, this vegetable oil has several beneficial effects in the obesity context by the reduction of lipid accumulation. Coconut oil can reduce lipid accumulation in hepatocytes and adipocytes. Coconut oil is capable of modulating the immune response in gut cells. 相似文献
11.
Effect of dietary taurine on bile acid metabolism in guinea pigs 总被引:1,自引:0,他引:1
The effect of oral administration of taurine (200–300 mg daily) on the metabolism of bile acids was studied in male guinea
pigs which have predominantly glycine conjugated bile acids. The results were summarized as follows: (a) oral administration
of taurine for 10 days increased taurine-conjugated bile acids and the ratio of glycine-to taurine-conjugated bile acids (G:T
ratio) shifted from 3.95 to 0.19; (b) in taurine fed guinea pigs, the half-life of chenodeoxycholic acid (CDC) was about 40%
shorter than that in controls and the fractional turnover rate increased by 70%; (c) the synthetic rate (mg/day/500 g body
weight) of bile acids increased from 4.28 to 7.27 by taurine feeding; (d) hepatic cholesterol 7α-hydroxylase activity was
increased 2.4-fold by taurine feeding; (e) the total pool size of bile acids did not change significantly but the amount of
lithocholic acid in the caecum and large intestine increased by about 40%; (f) neither free cholesterol nor cholesterol ester
levels in liver and serum changed significantly. Results of this study suggest that changing the G:T ratio in the bile acid
conjugation pattern may influence the rate of hepatic bile acid synthesis.
This paper is Part IX of a series entitled “Metabolism of Bile Acids”. Part VIII: ref. 12. 相似文献
12.
Meal fatty acids have been shown to modulate the size and composition of triacylglycerol (TAG)-rich lipoproteins influencing
the magnitude and duration of the postprandial plasma TAG response. As a result there is considerable interest in the origin
of these meal fatty-acid induced differences in particle composition. Caco-2 cells were incubated over 4 days with fatty acid
mixtures resembling the composition of saturated (SFA), monounsaturated (MUFA) and polyunsaturated fatty acid (PUFA)-rich
meals fed in a previous postprandial study to determine their impact on lipoprotein synthesis and secretion. The MUFA- and
PUFA-rich mixtures supported greater intracellular TAG, but not cholesterol accumulation compared with the SFA-rich mixture
(P < 0.001). The MUFA-rich mixture promoted significantly greater TAG and cholesterol secretion than the other mixtures and
significantly more apolipoprotein B-100 secretion than the PUFA-rich mixture (P < 0.05). Electron microscopy revealed the SFA-rich mixture had led to unfavourable effects on cellular morphology, compared
with the unsaturated fatty acid-rich mixtures. Our findings suggest the MUFA-rich mixture, may support the formation of a
greater number of TAG-rich lipoproteins, which is consistent with indirect observations from our human study. Our electron
micrographs are suggestive that some endocytotic uptake of MUFA-rich taurocholate micelles may promote greater lipoprotein
synthesis and secretion in Caco-2 cells. 相似文献
13.
14.
The effects of 1, 5, 10 and 20 μg/kg dosages of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) upon de novo fatty acid and cholesterol synthesis in liver and adipose tissue were determined in pair-fed rats.
The incorporation of tritium from3H2O into tissue lipids was measured. Hepatic and adipose fatty acid synthetic rates (μmoles acetyl units g−1 hr−1 in the control groups were 19.6±4 and 75.7±18.5, respectively, and the liver cholesterol synthetic rate was 2.9±0.5 TCDD
(1 μg/kg) inhibited fatty acid synthesis in the liver and adipose tissue, by 44% and 41% respectively, and the liver cholesterol
synthesis was inhibited by 37%. The extent of these inhibitions increased with increasing dosages of TCDD. The effect of TCDD
on sterol synthesis in adipose tissue could not be determined, because the tritium incorporation into the sterol fraction
in this tissue was not detectable. 相似文献
15.
It has been shown that tumor necrosis factor (TNF) rapidly upregulates expression of the low density lipoprotein (LDL) receptors
on Hep G2 cells and acutely stimulates hepatic lipid synthesis and secretionin vivo. It may thus be possible that TNF-induced expression of LDL receptors is secondary to a decrease in cellular cholesterol
content caused by TNF-stimulated lipid secretion. In order to know whether TNF upregulates LDL receptors by depletion of the
cellular cholesterol content, the present experiments were designed to study the temporal relationship between TNF-stimulated
expression of LDL receptor activity and TNF-induced changes in lipid synthesis and secretion in anin vitro setting by using Hep G2 cells (a highly differentiated human hepatoma cell line) as a hepatocyte model. Hep G2 cells were
incubated with TNF (usually 2.5 nmol/L) for certain periods, and LDL receptor activity was evaluated by measuring [125I]LDL binding at 4°C; lipid synthesis and secretion were assayed by measuring [3H]glycerol incorporation into triglycerides and phospholipids as well as [14C]acetate incorporation into cholesterol. We found that a 30-h exposure of the cells to TNF was needed for the effect of TNF
to be seen on lipid synthesis and secretion as measured by incorporation of [3H]glycerol into triglycerides and phospholipids, whereas TNF rapidly (in several hours) upregulated LDL receptor activity.
TNF stimulated triglyceride synthesis, but did not stimulate phospholipid synthesis. On the other hand, TNF stimulated phospholipid
secretion, but did not stimulate triglyceride secretion. Exposure of the cells to TNF for 16 or 24 h neither decreased cholesterol
synthesis nor stimulated cholesterol secretion as measured by [14C]acetate incorporation into cholesterol. Upregulation of LDL receptor activity through inhibition of cellular cholesterol
synthesis with compactin (a competitive inhibitor of the 3-hydroxyl-3-methylglutaryl-CoA reductase) was augmented by TNF,
whereas downregulation of LDL receptor activity through stimulation of cellular cholesterol synthesis with mevalonolactone
almost completely blocked the upregulatory effect of TNF. In conclusion, TNF-stimulated expression of LDL receptor activity
is not secondary to a depletion of cellular cholesterol content through TNF-stimulated lipid secretion or inhibition of cholesterol
synthesis. 相似文献
16.
Francesc Ibez Jorge Montesinos Estela Area-Gomez Consuelo Guerri María Pascual 《International journal of molecular sciences》2021,22(16)
Recent evidence pinpoints extracellular vesicles (EVs) as key players in intercellular communication. Given the importance of cholesterol and sphingomyelin in EV biology, and the relevance of mitochondria-associated endoplasmic reticulum membranes (MAMs) in cholesterol/sphingomyelin homeostasis, we evaluated if MAMs and sphingomyelinases (SMases) could participate in ethanol-induced EV release. EVs were isolated from the extracellular medium of BV2 microglia treated or not with ethanol (50 and 100 mM). Radioactive metabolic tracers combined with thin layer chromatography were used as quantitative methods to assay phospholipid transfer, SMase activity and cholesterol uptake/esterification. Inhibitors of SMase (desipramine and GW4869) and MAM (cyclosporin A) activities were also utilized. Our data show that ethanol increases the secretion and inflammatory molecule concentration of EVs. Ethanol also upregulates MAM activity and alters lipid metabolism by increasing cholesterol uptake, cholesterol esterification and SMase activity in microglia. Notably, the inhibition of either SMase or MAM activity prevented the ethanol-induced increase in EV secretion. Collectively, these results strongly support a lipid-driven mechanism, specifically via SMases and MAM, to explain the effect of ethanol on EV secretion in glial cells. 相似文献
17.
The regulation of cholesterol uptake and secretion by acylcoenzyme A:cholesterol acyltransferase (ACAT) was investigated in
the human intestinal cell line, CaCo-2. A new ACAT inhibitor, PD128042 (CI-976), was first characterized. The addition of
the fatty acid anilide to membranes prepared from CaCo-2 cells inhibited ACAT activity without altering the activities of
HMG-CoA reductase, fatty acid Co-A hydrolase, or triglyceride synthetase. PD128042 was a competitive inhibitor of ACTA with
50% inhibition occurring at a concentration of 0.2 μg/mL. When added to the medium of CaCo-2 cells at a concentration of 5
μg/mL, PD128042 inhibited oleate incorporation into cholesteryl oleate by 92% and increased oleate incorporation into triglycerides
and phospholipids by 51% and 38%, respectively. After incubating CaCo-2 cells with the ACAT inhibitor, the rate of newly synthesized
cholesterol decreased by 75% and membranes prepared from these cells contained significantly less HMG-CoA reductase activity.
PD128042 significantly decreased the basolateral secretion of newly synthesized cholesteryl esters without affecting the secretion
of newly synthesized triglycerides or phospholipids. The inhibitor decreased the esterification of labeled exogenous cholesterol
which was taken up by the cell from bile salt micelles. Moreover, after 16 hr of ACAT inhibition, less labeled unesterified
micellar cholesterol was associated with the cell. The esterification of cholesterol in CaCo-2 cells plays an integral role
in the uptake of cholesterol through the apical membrane and its eventual secretion at the basolateral membrane. 相似文献
18.
Chao-Rui Chen Ying-Nong Lee Chieh-Ming J. Chang Miau-Rong Lee I-Chien Wei 《Journal of the Chinese Institute of Chemical Engineers》2007,38(3-4):191-196
This work has examined the hot-pressurized fluid extraction of seven flavonoids, caffeic acid phenethyl ester and four phenolic acids from Brazilian propolis lumps generating, during the process, fat- and water-soluble extracts. The solid content of water-soluble extract obtained by hot-pressurized water in the presence of 29% natural surfactant was 35.2 mg/mL and was 44% greater than that obtained without natural surfactant. Furthermore the amount of the seven flavonoids and caffeic acid phenethyl ester in the fat-soluble extract exceeded those in the water-soluble sample while, on the other hand, the amount of the four phenolic acids in the water-soluble extract was more than those in the fat-soluble extract. Our findings show that the total solid content and the amount of these 12 active compounds produced by the emulsified hot-pressurized water are 36% and 7% higher, respectively, than those produced by emulsified water at atmospheric pressure. The EC50 value of the free radical scavenging activity of 1,1-diphenyl-2-picrylhydrazyl of the emulsified hot-pressurized water extract was the lowest, and presented the strongest anti-oxidation ability among all the extracts. In vitro cytotoxicity indicated that the water-soluble extract strongly suppressed the growth of leukemia (HL-60, U937), lung cancer (A549, CH27) and liver cancer (Hep G2, Hep 3B) cells in a concentration-dependent behavior. 相似文献
19.
David Andersson ke Nilsson Rui‐Dong Duan 《European Journal of Lipid Science and Technology》2006,108(2):103-108
Purpose: Alkaline sphingomyelinase (alk‐SMase) is an enzyme that hydrolyses sphingomyelin in a bile salt‐dependent manner in the gastrointestinal tract, and has been proposed as an inhibitor of colon carcinogenesis. Ursolic acid (UA) is a plant‐derived pentacyclic triterpenoid that has been shown to have anti‐proliferative and apoptotic effects on HT29 human colon adenocarcinoma cells, with activation of alk‐SMase as an early event. The aim of this study was to study the in vitro effects of UA and its analogues on the activity of purified rat intestinal alk‐SMase. Methods: Rat intestinal alk‐SMase activity was determined after incubation with UA in the presence and absence of taurocholate (TC). The effect was compared with boswellic acids, another group of pentacyclic triterpenoids. Results: UA enhanced the activity of rat intestinal alk‐SMase in a dose‐dependent manner, without a similar effect on bacterial neutral SMase. Four types of boswellic acid also increased the enzyme activity, with the effect of acetyl‐keto‐β‐boswellic acid being most potent. Activation of alk‐SMase by TC at a low concentration (0.4 mM), but not at a high concentration, was enhanced by UA. Conclusions: Ursolic acid and four types of boswellic acid, all pentacyclic triterpenoids, have a stimulatory effect on the activity of intestinal alk‐SMase. 相似文献
20.
The addition of ascorbic acid (20–160 μg) to mitochondrial preparations of rat or guinea pig liver has no effect upon the
oxidation of [26-14C]-cholesterol to14CO2. The 7α-hydroxylation of cholesterol by rat liver microsomes is also unaffected by addition of ascorbic acid. Hydroxylation
by guinea pig liver microsomes is increased in the presence of ascorbic acid, but the results are not statistically significant. 相似文献