• Title/Summary/Keyword: Apolipoprotein A

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Apolipoprotein A5 3'-UTR variants and cardiometabolic traits in Koreans: results from the Korean genome and epidemiology study and the Korea National Health and Nutrition Examination Survey

  • Kim, Oh Yoen;Moon, Jiyoung;Jo, Garam;Kwak, So-Young;Kim, Ji Young;Shin, Min-Jeong
    • Nutrition Research and Practice
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    • v.12 no.1
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    • pp.61-68
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    • 2018
  • BACKGROUND/OBJECTIVES: This study aimed to test the association between APOA5 3'-UTR variants (rs662799) and cardiometabolic traits in Koreans. SUBJECTS/METHODS: For this study, epidemiological data, Apolipoprotein A5 (APOA5) genotype information, and lymphoblastoid cell line (LCL) biospecimens from a subset of the Ansung-Ansan cohort within the Korean Genome and Epidemiology study (KoGES-ASAS; n = 7,704) as well as epidemiological data along with genomic DNA biospecimens of participants from a subset of the Korea National Health and Nutrition Examination Survey (KNHANES 2011-12; n = 2,235) were obtained. APOA5 mRNA expression was also measured. RESULTS: APOA5 rs662799 genotype distributions in both the KoGES-ASAS and KNHANES groups were 50.6% for TT, 41.3% for TC, and 8.1% for CC, which are similar to those in previous reports. In both groups, minor C allele carriers, particularly subjects with CC homozygosity, had lower high-density lipoprotein (HDL) cholesterol and higher triglyceride levels than TT homozygotes. Linear regression analysis showed that the minor C allele significantly contributed to reduction of circulating HDL cholesterol levels [${\beta}=-2.048$, P < 0.001; ${\beta}=-2.199$, P < 0.001] as well as elevation of circulating triglyceride levels [${\beta}=0.053$, P < 0.001; ${\beta}=0.066$, P < 0.001] in both the KoGES-ASAS and KNHANES groups. In addition, higher expression levels of APOA5 in LCLs of 64 healthy individuals were negatively associated with body mass index (r = -0.277, P = 0.027) and circulating triglyceride level (r = -0.340, P = 0.006) but not significantly correlated with circulating HDL cholesterol level. On the other hand, we observed no significant difference in the mRNA level of APOA5 according to APOA5 rs662799 polymorphisms. CONCLUSIONS: The C allele of APOA5 rs662799 was found to be significantly associated with cardiometabolic traits in a large Korean population from the KoGES-ASAS and KNHANES. The effect of this genotype may be associated with post-transcriptional regulation, which deserves further experimental confirmation.

Susceptibility of Mice to Trypanosoma evansi Treated with Human Plasma Containing Different Concentrations of Apolipoprotein L-1

  • Da Silva, Aleksandro S.;Fanfa, Vinicius R.;Otto, Mateus A.;Gressler, Lucas T.;Tavares, Kaio C.S.;Lazarotto, Cicera R.;Tonin, Alexandre A.;Miletti, Luiz C.;Duarte, Marta M.M.F.;Monteiro, Silvia G.
    • Parasites, Hosts and Diseases
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    • v.49 no.4
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    • pp.427-430
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    • 2011
  • The aim of this study was to test the susceptibility of mice to Trypanosoma evansi treated with human plasma containing different concentrations of apolipoprotein L-1 (APOL1). For this experiment, a strain of T. evansi and human plasma (plasmas 1, 2, and 3) from 3 adult males clinically healthy were used. In vivo test used 50 mice divided in 5 groups (A to E) with 10 animals in each group. Animals of groups B to E were infected, and then treated with 0.2 ml of human plasma in the following outline: negative control (A), positive control (B), treatment with plasma 1 (C), treatment with plasma 2(D), and treatment with plasma 3 (E). Mice treated with human plasma showed an increase in longevity of $40.9{\pm}0.3$ (C), $20{\pm}9.0$ (D) and $35.6{\pm}9.3$ (E) days compared to the control group (B) which was $4.3{\pm}0.5$ days. The number of surviving mice and free of the parasite (blood smear and PCR negative) at the end of the experiment was 90%, 0%, and 60% for groups C, D, and E, respectively. The quantification of APOL1 was performed due to the large difference in the treatments that differed in the source plasma. In plasmas 1, 2, and 3 was detected the concentration of 194, 99, and 115 mg/dl of APOL1, respectively. However, we believe that this difference in the treatment efficiency is related to the level of APOL1 in plasmas.

Increased Frequency of Apolipoprotein E4 Genotype in Childhood Minimal Change Nephrotic Syndrome (MCNS) (소아 미세변화 신증후군 환자에서 Apolipoprotein E4 유전자형에 관한 연구)

  • Kim Sung-Do;Bae Young-Min;Cho Byoung-Soo;Cho Yoe-Won;Kim Il-Soo
    • Childhood Kidney Diseases
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    • v.5 no.2
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    • pp.87-99
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    • 2001
  • Purpose: We studied to find out apo-E genotype polymorphism in minimal change nephrotic syndrome(MCNS) and IgA nephropathy(IgAN) and to determine the relationship between apo-E genotype and clinical course of MCNS. Materials and Method: 43 MCNS patients and 15 IgAN patients were examined for apo-E polymorphism. 50 healthy blood donors were examined for apo-E genotype as control. Genomic DNA was prepared front peripheral blood leukocytes according to standard procedures. Results: As compared with control group, e4 allele frequency was significantly increased in MCNS (p<0.01). However, in IgAN e2 allele frequency, however, was 2.6 times higher than normal control (P<0.01). The frequency of e4 allele of frequent relapser group was 4.6 times higher than normal control and was 2 times higher than infrequent relapser group. Conclusion: We think that apo-E typing might be one of the parameters, which should be considered to predict the course of MCNS in children. MCNS with risky HLA profile and E4/4 genotype could indicate the need for a longer steroid administration. And apo-E genotype needs to be considered for the evaluation of therapeutic responses to other drugs. (J, Korean Soc Pediatr Nephrol 2001 ; 5 : 87-99)

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Human Apolipoprotein E2 Transgenic Mice Show Lipid Accumulation in Retinal Pigment Epithelium and Altered Expression of VEGF and bFGF in the Eyes

  • Lee, Sung-Joon;Kim, Jeong-Hun;Kim, Jin-Hyoung;Chung, Mi-Ja;Wen, Qingcheng;Chung, Hum;Kim, Kyu-Won;Yu, Young-Suk
    • Journal of Microbiology and Biotechnology
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    • v.17 no.6
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    • pp.1024-1030
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    • 2007
  • We investigated the human apolipoprotein E2 (apoE2) transgenic mouse as an animal model system for age-related macular degeneration (AMD). Transgenic mice expressing human apoE2 and C57BL/6J mice were fed normal chow or a high-fat diet for 4 weeks. Eyes were collected from the mice and lipid deposits in retinal pigment epithelium (RPE) were assessed using electron microscopy. The expressions of apoE, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and pigment-epithelium derived factor (PEDF), which are molecular markers for angiogenesis, were assessed with immunohistochemistry. Eyes from apoE2 mice, regardless of diet, contained lipid accumulation in RPE under electron microscopy, whereas control C57BL/6J eyes did not. Lipid accumulation was found predominantly in the RPE and the Bruch's membrane and increased in the eyes of apoE2 mice after one month of a high-fat diet ($8{\pm}2\;per\;50{\mu}m^2$ for normal chow and $11{\pm}2\;per\;50\;{\mu}m^2,\;p<0.05)$. ApoE expression was similar in the apoE2 and control mice; however, VEGF and bFGF were overexpressed in the retinal pigment epithelium of apoE2 eyes compared with control eyes, and PEDF expression was slightly decreased. These expression patterns of VEGF, bFGF, and PEDF suggest angiogenesis is progressing in apoE2 eyes. In conclusion, the eyes of apoE2 mice develop typical lipid accumulations, a common characteristic of AMD, making them a suitable animal model for AMD. The expression profile of VEGF and bFGF on the retinal pigment epithelium suggests that apoE2 may induce neovascularization by altering angiogenic cytokines.

Cholesterol Improvement Synergistic Effects of Fermented Soybean Grits Caused by Added with Mung Bean in vitro (녹두 첨가로 인한 탈지대두 Grits(Defatted Soybean Grits) 발효물의 in vitro 상에서의 콜레스테롤 개선능 상승효과)

  • Lee, Sung-Gyu;Kim, Hyun-Jeong;Yu, Mi-Hee;Lee, Eun-Ju;Lee, Sam-Pin;Lee, In-Seon
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.39 no.7
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    • pp.947-952
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    • 2010
  • This study was performed to investigate cholesterol improvement of fermented defatted soybean grits (FD) and FD added with 2.5, 5, 10% mung bean (FDM). The FD and FDM were prepared by the solid state fermentation using Bacillus subtilis NUC1 at $40^{\circ}C$ for 24 hr. More than 70% cholesterol adsorption of FD and FDM groups was shown. Particularly, FDM added with 2.5% mung bean (2.5% FDM) showed highest cholesterol adsorption by 90% among FD and FDM groups. 2.5% FDM showed 42% inhibition effect on HMG-CoA reductase, and significantly decreased the intracellular cholesterol contents in HepG2 cells. Apolipoprotein AI, CIII improvement effects of FD and FDM group in HepG2 cells showed most effects in the 2.5% FDM. The results suggest that FDM added with 2.5% mung bean may be beneficial to the prevention of hypercholesterol.

Statistical Selection of Amino Acids Fortifying a Minimal Defined Medium for a High-level Production of the Kringle Fragments of Human Apolipoprotein(a)

  • Lim, Hyung-Kwon;Kim, Sung-Geun;Jung, Kyung-Hwan;Seo, Jin-Ho
    • Journal of Microbiology and Biotechnology
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    • v.14 no.1
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    • pp.90-96
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    • 2004
  • A synthetic defined medium, fortified with amino acids, was developed for the stable production of the kringle fragments of human apolipoprotein(a) (apo(a)), rhLK68. Using a complex rich medium containing yeast extract and a high-cell-density fed-batch culture, the expression level of rhLK68 reached 17% of the total cellular protein, which corresponded to $5\;g\;l^{-1}$ of the culture. To replace the complex media with chemically defined media, several amino acids that positively affect cell growth and gene expression were chosen by a statistical method. The various combinations of the selected amino acids were tested for its fortifying effect on a minimal defined medium. When glutamine only was added, the overall expression level of rhLK68 reached 93% of the complex rich medium increasing the specific expression level by 22.4% and decreasing the cell growth by 24%. Moreover, the addition of glutamine resulted in a 2-fold increase in the concentration of rhLK68 in the culture broth, compared with the minimal defined medium. The synthetic defined media developed in this study could be generally applied to high-cell-density cultures of the recombinant Escherichia coli BL21(DE3), especially for the production of therapeutic proteins that require a strict quality control of the culture media and fermentation processes.

LJ-1888, a selective antagonist for the A3 adenosine receptor, ameliorates the development of atherosclerosis and hypercholesterolemia in apolipoprotein E knock-out mice

  • Park, Jong-Gil;Jeong, Se-Jin;Yu, Jinha;Kim, Gyudong;Jeong, Lak Shin;Oh, Goo Taeg
    • 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.

Measurement of the Affinity Constant of Monoclonal Antibody to Human Apolipoprotein A-I by ELISA (효소면역 분석법에 의한 아포지단백질 A-I 단일클론항체의 친화상수의 측정)

  • Mic Hung Yoon;Hyun Hee Lee
    • Biomedical Science Letters
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    • v.1 no.1
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    • pp.1-8
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    • 1995
  • The present study was undertaken to determine the dissociation constant (Kd)of monoclonal antibody to human apolipoprotein A-I (apo A-I) using enzyme-linked immunosorbent assay (ELISA). First the monoclonal antibody was incubated in solution with the antigen until the equilibrium was reached; then the free antibody which remains unsaturated at equilibrium was captured by binding to antigen on the microtiter plate and be measured by a classical indirect ELISA. The value of Kd determined from Scatchard plot was 0.625$\times$10^{-9}$ for purified antibody and 0.720$\times$10$^{-9}$ for unpurified antibody. This method was valuable for the measurement of true dissociation constant and found to be simple, reproducible, and accurate.

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The involvement of ginseng berry extract in blood flow via regulation of blood coagulation in rats fed a high-fat diet

  • Kim, Min Hee;Lee, Jongsung;Jung, Sehyun;Kim, Joo Wan;Shin, Jae-Ho;Lee, Hae-Jeung
    • Journal of Ginseng Research
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    • v.41 no.2
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    • pp.120-126
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    • 2017
  • Background: The present study investigated the effect of ginseng berry hot water extract (GBx) on blood flow via the regulation of lipid metabolites and blood coagulation in rats fed a high-fat diet (HFD). Methods: Sixty rats were divided into five groups in descending order of body weight. Except for the control group, the other four groups were fed a HFD containing 45% kcal from fat for 11 wk without GBx. GBx groups were then additionally treated by gastric gavage with GBx dissolved in distilled water at 50 (GBx 50) mg/kg, 100 (GBx 100) mg/kg, or 150 (GBx 150) mg/kg body weight for 6 wk along with the HFD. To investigate the effects of GBx on rats fed a HFD, biochemical metabolite, blood coagulation assay, and histological analysis were performed. Results: In the experiments to measure the serum levels of leptin and apolipoprotein B/A, GBx treatment attenuated the HFD-induced increases in these metabolites (p < 0.05). Adiponectin and apolipoprotein E levels in GBx-treated groups were significantly higher than the HFD group. Prothrombin time and activated partial thromboplastin time were increased in all GBx-treated groups. In the GBx-treated groups, the serum levels of thromboxane $A_2$ and serotonin were decreased and concentrations of serum fibrinogen degradation products were increased (p < 0.05). Moreover, histomorphometric dyslipidemia-related atherosclerotic changes were significantly improved by treatment with GBx. Conclusion: These results suggest the possibility that GBx can ameliorate blood flow by decreasing intima-media thickness via the regulation of blood coagulation factors related to lipid metabolites in rats fed a HFD.