• Preventive Nutrition and Food Science
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• v.4 no.2
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• pp.145-151
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• 1999

Apolipoprotein B-100 (apo B-100) is an important component in plasma low density lipoproteins (LDL). It function as the ligand for the LDL receptor in peripheral cells. The LDLs are removed from the circulation by both high-affinity receptor-mediated and receptor-independant pathways. LDLs are heterogeneous in their lipid content, size and density and certain LDL subspecies increase risk of atherosclerosis due to differences in the conformation of apo B in the particle. In the present study , surface and core peptide fraction of Apo B-100 have been characterized by comparing peptide-mapping and fluorescence spectroscopy. Surface fragments of apo B-100 were generated by digestion of LDL with either trypsin , pronase, or pancreatin elastase. Surface fractions were fractionated on a Sephadex G-50 column. The remaining core fragments were delipidated and redigested with the above enzymes, and the resulting core peptides were compared with surface peptides. Results from peptide-mapping by HPLC showed pronase-digestion was more extensive than trypsin -digestion to remove surface peptide fraction from LDL. Fluorescence spectra showed that core fractions contained higher amount of tryptophan than surface fractions, and it indicated that core fraction wa smore hydrophobic than surface fractions. A comparison of the behavior of the core and surface provided informations about the regions of apo B-100 involved in LDL metabolism and also about the structural features concerning the formation of atherosclerosis.

• Biomolecules & Therapeutics
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• v.15 no.3
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• pp.162-168
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• 2007

It is well known that oxidized low-density lipoprotein (oxLDL) is the most characterized humoral factor that plays an important role in the pathogenesis of atherosclerosis. The water extract of the Korean herbal remedy, ZoaGumHwan (ZGH), which is composed of roots of Coptis chinensis Franch and fruits of Evodia officinalis Dode with the ratio of 6 to 1, reduced the in vitro oxidation of low density lipoproteins (LDL). Also, the ZGH extract and berberine, one of the major components of ZGH, significantly prevented oxLDL-induced adhesion of monocytes to human umbilical vein endothelial cells (HUVEC). Furthermore, the ZGH water extract and berberine decreased oxLDL-induced expression of CC chemokine receptor 2 (CCR2), a dominant monocyte chemotaxis receptor, in U937 human monocytic cells. The protective effects of the ZGH water extract and berberine were similar to those of simvastatin, an effective lipid-lowering drug. The results suggest that Korean herbal remedy, ZGH, seems to have protective effect against oxLDL-induced monocyte chemoattractant protein (MCP)-1/CCR2-dependent monocyte recruitment onto endothelial cells.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.3
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• pp.235-240
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• 2015

Androgen receptor (AR) signaling is important for prostate cancer (PCa) cell proliferation. Here, we showed that proliferation of hormone-sensitive prostate cancer cells such as LNCaP was significantly enhanced by testosterone stimulation whereas hormone-insensitive prostate cancer cells such as PC3 and VCaP did not respond to testosterone stimulation. Blocking of AR using bicalutamide abolished testosterone-induced proliferation of LNCaP cells. In addition, knockdown of AR blocked testosterone-induced proliferation of LNCaP cells. Basal expression of low-density lipoprotein receptor-related protein 6 (LRP6) was elevated in VCaP cells whereas stimulation of testosterone did not affect the expression of LRP6. However, expression of LRP6 in LNCaP cells was increased by testosterone stimulation. In addition, knockdown of LRP6 abrogated testosterone-induced proliferation of LNCaP cells. Given these results, we suggest that androgen-dependent expression of LRP6 plays a crucial role in hormone-sensitive prostate cancer cell proliferation.

• Nutrition Research and Practice
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• v.12 no.4
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• pp.298-306
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• 2018

BACKGROUND/OBJECTIVES: Obesity is a global health problem of significant importance which increases mortality. In place of anti-obesity drugs, natural products are being developed as alternative therapeutic materials. In this study, we investigated the effect of Brassica juncea L. leaf extract (BLE) on fat deposition and lipid profiles in high-fat, high-cholesterol diet (HFC)-induced obese rats. MATERIALS/METHODS: Male Sprague-Dawley rats were divided into four groups (n = 8 per group) according to diet: normal diet group (ND), high-fat/high-cholesterol diet group (HFC), HFC with 3% BLE diet group (HFC-A1), and HFC with 5% BLE diet group (HFC-A2). Each group was fed for 6 weeks. Rat body and adipose tissue weights, serum biochemical parameters, and tissue lipid contents were determined. The expression levels of mRNA and proteins involved in lipid and cholesterol metabolism were determined by reverse transcription polymerase chain reaction and western blot analysis, respectively. RESULTS: The HFC-A2 group showed significantly lower body weight gain and food efficiency ratio than the HFC group. BLE supplementation caused mesenteric, epididymal, and total adipose tissue weights to decrease. The serum levels of triglyceride, total cholesterol, and low-density lipoprotein cholesterol were significantly reduced, and high-density lipoprotein cholesterol was significantly increased in rats fed BLE. These results were related to lower glucose-6-phosphate dehydrogenase, acetyl-coA carboxylase, and fatty acid synthase mRNA expression, and to higher expression of the cholesterol $7{\alpha}$-hydroxylase and low density lipoprotein-receptor, as well as increased protein levels of peroxisome proliferator-activated receptor ${\alpha}$. Histological analysis of the liver revealed decreased lipid droplets in HFC rats treated with BLE. CONCLUSIONS: Supplementation of HFC with 3% or 5% BLE inhibited body fat accumulation, improved lipid profiles, and modulated lipogenesis- and cholesterol metabolism-related gene and protein expression.

• Molecules and Cells
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• v.26 no.4
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• pp.409-414
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• 2008

The cholesteryl ester transfer protein (CETP), a key player in cholesterol metabolism, has been shown to promote the transfer of triglycerides from very low density lipoprotein (VLDL) and low density lipoprotein (LDL) to high density lipoprotein (HDL) in exchange for cholesterol ester. Here we demonstrate that farnesoid X receptor ${\alpha}$ ($FXR{\alpha}$; NR1H4) down-regulates CETP expression in HepG2 cells. A $FXR{\alpha}$ ligand, chenodeoxycholic acid (CDCA), suppressed basal mRNA levels of the CETP gene in HepG2 cells in a dose-dependent manner. Using gel shift and chromatin immunoprecipitation (ChIP) assays, we found that $FXR{\alpha}$ could bind to the liver X receptor ${\alpha}$ ( $LXR{\alpha}$; NR1H3) binding site (LXRE; DR4RE) located within the CETP 5' promoter region. $FXR{\alpha}$ suppressed $LXR{\alpha}$-induced DR4RE-luciferase activity and this effect was mediated by a binding competition between $FXR{\alpha}$ and $LXR{\alpha}$ for DR4RE. Furthermore, the addition of CDCA together with a $LXR{\alpha}$ ligand, GW3965, to HepG2 cells was shown to substantially decrease mRNA levels of hepatic CETP gene, which is typically induced by GW3965. Together, our data demonstrate that $FXR{\alpha}$ down-regulates CETP gene expression via binding to the DR4RE sequence within the CETP 5' promoter and this $FXR{\alpha}$ binding is essential for $FXR{\alpha}$ inhibition of $LXR{\alpha}$-induced CETP expression.

• Proceedings of the KSAR Conference
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• 2002.06a
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• pp.82-82
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• 2002

The Wnt signaling pathway plays pivotal roles in embryonic development and oncogenesis through various signaling molecules inculding Frizzled receptor, recently characterized LRP5/6 and Dickkopf protein. Although Wnt signaling has been characterized in both developmental and oncogenic processes, little is known about its function in the normal adult. The ability of LRP5 to bind apolipoprotein E(apoE) and the abundant expression of LRP5 transcripts in hepatocytes, raise the possibility that LRP5 plays a role in the hepatic clearance of ApoE-containing chylomicron remonants, a major plasma lipoprotein carrying diet-derived cholesterol. (omitted)

• Journal of the Korean Society of Food Science and Nutrition
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• v.24 no.3
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• pp.362-370
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• 1995

Human plasma low density lipoprotein(LDL) is the main carrier for cholesterol, and recent studies suggest the normal LDL can be readily oxidized by free radical and not interact with LDL receptor. Lipoprotein pariticles are consisted of lipid andprotein, and fatty acids of lipoproteins are prone to oxidation. LDL particles readily undergo oxidative modification by copper. From the results, oxidized LDL altered its biological properties. A marked increase in the electrophoretic mobility of LDl on agarose gel indicated that negative surface charge of the LDL particles was increased. Also, the results from the HPLC showed that oxidized LDL was degraded into several polypeptides nonenzymatically. Degradation tests which measured the amount of 5-IAF labelled oxidized LDL were carried out by monocyte and hepatocyte cell culture. Hepatocyte cell culture of modified LDL did not show consistent pattern. However, binding rate of modified LDL with HMDM(human monocyte derived macrophage) was enhanced with oxidation, but was retarded by addition of antioxidants(hyaluronic acid, vitamin A, vitamin E). Also comparisons of oxidized-LDL, acetyl-LDL and MDA-LDL showed significant differences in the chemical properteis and binding affinity to HMDM. Thus, modificaition of normal LDL altered its biological properties.

• BMB Reports
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• v.51 no.10
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• pp.520-525
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• 2018

Cardiovascular diseases arising from atherosclerosis are the leading causes of mortality and morbidity worldwide. Lipid-lowering agents have been developed in order to treat hypercholesterolemia, a major risk factor for atherosclerosis. However, the prevalence of cardiovascular diseases is increasing, indicating a need to identify novel therapeutic targets and develop new treatment agents. Adenosine receptors (ARs) are emerging as therapeutic targets in asthma, rheumatoid arthritis, cancer, ischemia, and inflammatory diseases. This study assessed whether LJ-1888, a selective antagonist for $A_3$ AR, can inhibit the development of atherosclerosis in apolipoprotein E knock-out ($ApoE^{-/-}$) mice who are fed a western diet. Plaque formation was significantly lower in $ApoE^{-/-}$ mice administered LJ-1888 than in mice not administered LJ-1888, without any associated liver damage. LJ-1888 treatment of $ApoE^{-/-}$ mice prevented western diet-induced hypercholesterolemia by markedly reducing low-density lipoprotein cholesterol levels and significantly increasing high-density lipoprotein cholesterol concentrations. Reduced hypercholesterolemia in $ApoE^{-/-}$ mice administered LJ-1888 was associated with the enhanced expression of genes involved in bile acid biosynthesis. These findings indicate that LJ-1888, a selective antagonist for $A_3$ AR, may be a novel candidate for the treatment of atherosclerosis and hypercholesterolemia.

• Journal of Microbiology and Biotechnology
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• v.34 no.2
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• pp.425-435
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• 2024

Schisandra chinensis extract (SCE) protects against hypocholesterolemia by inhibiting proprotein convertase subtilisin/kexin 9 (PCSK9) protein stabilization. We hypothesized that the hypocholesterolemic activity of SCE can be attributable to upregulation of the PCSK9 inhibition-associated low-density lipoprotein receptor (LDLR). Male mice were fed a low-fat diet or a Western diet (WD) containing SCE at 1% for 12 weeks. WD increased final body weight and blood LDL cholesterol levels as well as alanine transaminase and aspartate aminotransferase expression. However, SCE supplementation significantly attenuated the increase in blood markers caused by WD. SCE also attenuated WD-mediated increases in hepatic LDLR protein expression in the obese mice. In addition, SCE increased LDLR protein expression and attenuated cellular PCSK9 levels in HepG2 cells supplemented with delipidated serum (DLPS). Non-toxic concentrations of schisandrin A (SA), one of the active components of SCE, significantly increased LDLR expression and tended to decrease PCSK9 protein levels in DLPS-treated HepG2 cells. High levels of SA-mediated PCSK9 attenuation was not attributable to reduced PCSK9 gene expression, but was associated with free PCSK9 protein degradation in this cell model. Our findings show that PCSK9 secretion can be significantly reduced by SA treatment, contributing to reductions in free cholesterol levels.

• Journal of the Korean Society of Food Science and Nutrition
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• v.42 no.6
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• pp.861-868
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• 2013

This study investigated the effects of Opuntia ficus-indica and other natural resources (OF) in db/db and C57 mice. Plasma triglycerides, cholesterol, alanine aminotransferase (ALT) activity, aspartate aminotransferase (AST) activity, fecal bile acid excretion, the histopathological appearance of the liver, and cholesterol-related mRNA expression were determined. Mice (12 db/db mice and 12 C57 mice) were assigned to diabetic-control (db-C), diabetic-OF treatment (db-OF), normal-control (C57-C), and normal-OF treatment (C57-OF) groups. Animals in the control group were fed an AIN-76 recommended diet and animals in the OF group were fed an experimental diet containing 5% of OF for 4 weeks. Concentrations of total plasma cholesterol, triglyceride, low density lipoprotein (LDL)-cholesterol, and very low density lipoprotein (VLDL)-cholesterol decreased with the administration of OF. In contrast, high density lipoprotein (HDL)-cholesterol levels were minimally affected by the experimental diet. Plasma AST and ALT showed lower activities in the db-OF group, and the fecal excretion of bile acid was reduced in the db-OF group. Histopathological analysis of the liver showed that fatty liver conditions in the db-OF group were more improved than db-C. Low-density lipoprotein receptor (LDL-R) and cholesterol 7${\alpha}$-hydroxylase (CYP7A1) mRNA expression were increased in the db-OF group as well. However, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA-R) mRNA expression was lower in the db-OF group. These results provide experimental evidence about improved lipid metabolism of the OF feeding in the db/db mice.