• Title/Summary/Keyword: apoB

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The Structural Studies of Peptide P143 Derived from Apo B-100 by NMR

  • Lee, Ji-Eun;Kim, Gil-Hoon;Won, Ho-Shik
    • Journal of the Korean Magnetic Resonance Society
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    • v.25 no.4
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    • pp.58-63
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    • 2021
  • Apolipoprotein B-100 (apo B-100), the main protein component that makes up LDL (Low density lipoprotein), consists of 4,536 amino acids and serves to combine with the LDL receptor. The oxidized LDL peptides by malondialdehyde (MDA) or acetylation in vivo act as immunoglobulin (Ig) antigens and peptide groups were classified into 7 peptide groups with subsequent 20 amino acids (P1-P302). The biomimetic peptide P143 (IALDD AKINF NEKLS QLQTY) out of C-group peptides carrying the highest value of IgG antigens were selected for structural studies that may provide antigen specificity. Experimental results show that P143 has β-sheet in Ile[1]-Asn[9] and α-helice in Gln[16]-Tyr[20] structure. Homonuclear 2D-NMR (COSY, TOCSY, NOESY) experiments were carried out for NMR signal assignments and structure determination for P143. On the basis of these completely assigned NMR spectra and proton distance information, distance geometry (DG) and molecular dynamic (MD) were carried out to determine the structures of P143. The proposed structure was selected by comparisons between experimental NOE spectra and back-calculated 2D NOE results from determined structure showing acceptable agreement. The total Root-Mean-Square-Deviation (RMSD) value of P143 obtained upon superposition of all atoms were in the set range. The solution state P143 has a mixed structure of pseudo α-helix and β-turn(Phe[10] to Glu[12]). These results are well consistent with calculated structure from experimental data of NOE spectra. Structural studies based on NMR may contribute to the prevent oxidation studies of atherosclerosis and observed conformational characteristics of apo B-100 in LDL using monoclonal antibodies.

Anti-atherosclerotic Effect of Green Tea in Poluynsaturated Fatty Acids-treated Apo E KO Mice (식이불포화지방산을 섭취한 Apo E KO Mice에서의 녹차의 항동맥경화억제 효과)

  • Kim, Hyo-Sook;Lee, Myoung-Sook
    • Journal of Nutrition and Health
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    • v.44 no.6
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    • pp.465-473
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    • 2011
  • Dietary fatty acids are under intense research to identify anti-atherogenic mechanisms, so we investigated green tea powder (GT) as a protector against atherogenesis originating from lipid peroxidation such as 4-hydroxynonemal (4-HNE) and malondialdehyde (MDA) in different dietary fatty acid-treated apo E KO mice. Growth rate and dietary efficiency were lower in apo E KO mice with or without LA compared to wild type. Plasma total cholesterol (TC) and triacylglycerol (TG) did not correspond to values in other tissues, but TG in heart tissue decreased significantly by GT after linoleic acid (LA) or docosahexaenoic acid (DHA) was administered. LA induced apoptosis as evidenced by changes in aorta morphology and immunohistochemistry. Lipid peroxides (LPO) was increased in apo E KO mice with or without LA corresponding to the accumulation of 4-HNE or MDA in the proximal aorta above the atria. GT consumption tended to reduce the primary causal mechanism of atherogenic phenomena such as oxidizability in both LA and DHA treated atherogenic mice. A high polyunsaturated fatty acids (PUFA) diet involved the changes on stress-induced apoptotic signaling by increasing caspase 3, cytochrome c, and nuclear factor-${\kappa}B$ in the heart tissue, but decreasing the bcl-2 protein. However, GT remarkably reduced the expression of apoptotic signaling, in contrast to the PUFA diet. Therefore, the potential of GT as an anti-atherosclerotic dietary antioxidant was tested in this study.

Genetic Variation in Exon 3 of Human Apo B mRNA Editing Protein (apobec-1) Gene

  • Hong, Seung-Ho;Song, Jung-Han;Kim, Jin-Q
    • Journal of Genetic Medicine
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    • v.3 no.1
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    • pp.15-19
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    • 1999
  • We have investigated the genetic variation in the human apo B mRNA editing protein (apobec-1) gene. Exon 3 of the apobec-1 gene was amplified by polymerase chain reaction. After detection of an additional band by single strand conformational polymorphism (SSCP) analysis, sequencing of the SSCP-shift sample revealed a single-base mutation. The mutation was a CGG transversion at codon 80 resulting in a lleRMet substitution. This substitution was confirmed by restriction fragment length polymorphism analysis since a Pvull site is abolished by the substitution. Population and family studies confirmed that the inheritance of the genotypes for apobec-1 gene polymorphism is controlled by two codominant alleles (P1 and P2). A significant difference in plasma triglyceride was detected among the different apobec-1 genotypes in the CAD patients (P<0.05). Our study could provide the basis for elucidating the interaction between genetic variation of the apobec-1 gene and disorders related to lipid metabolism.

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Differential Effect of n6 and n3 Polyunsaturated Fatty Acids on Plasma Lipids in Rats Fed Low and High Fat Diets (식이지방 수준에 따라 n6 와 n3 계 불포화지방산이 혈장 지질수준에 미치는 영향에 관한 비교연구)

  • Nam, Jung-He;Park, Hyun-Suh
    • Journal of Nutrition and Health
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    • v.24 no.4
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    • pp.314-325
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    • 1991
  • To compare the hypolipidemic effects of n6 and n3 PUFA at different fat levels, male Sprague Dawley rats were fed either low fat (LF, 10% Cal) or high fat (HF, 40% Cal) diet which was different only in fatty acid composition for 6 weeks. Dietary fats were beef tallow, corn oil, perilla oil, and fish oil concentrate as a source of saturated fatty acid, n6 linoleic acid(LA). n3 ${\alpha}-linolenic$ acid(LL) and n3 eicosapentaenoic acid(EPA)+docosahexaenoic acid(DHA), respectively. VLDL fraction was separated by ultracentrifugation and chemical composition was determined by thin layer chromatography. Plasma cholesterol level was increased by n6 LA but decreased by n3 LL and n3 EPA in LF and HF diets, and the hypocholesterolemic effect of n3 EPA was most significant in HF diet. HDL-Chol level was raised by n6 LA in LF and HF diets, but significantly reduced by n3 EPA in HF. Plasma TG level was reduced by n6 LA n3 LL and EPA in LF and HF with the reduction of lipogenic enzyme activity only by n3 PUFAs. The proportion of TG in VLDL fraction was significantly lowered by n3 EPA in LF and HF. The proportion of apo-B in VLDL fraction was not changed in LF, but was significantly decreased in HF by n3 EPA. Therefore, the hypotriglyceridemic effect of n3 PUFA could be from the reduced lipogenesis in liver and resulted in the depressed secretion of TG as VLDL in LF and HF with significant lower production of apoB in HF diet.

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HMGCoA reductase inhibitor의 혈청 지질 개선효과

  • 이명묵
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1994.04a
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    • pp.332-332
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    • 1994
  • 식이습관을 바꾸지 않는 상태에서 4주간의 placebo 투여후 혈청 Total-C치가 240mg/dl 이상인 원발성 고콜레스테 혈증환자 25예씩 두군으로 하여 제1군은 lovastatin 20mg에서 80mg을 1일 1회 저녁에 12주간 투여하였고, 제2군은 pravastatin 5mg을 12주간 아침 저녁으로 2회 경구 투여하였다. Lovastatin과 pravastatin 12주 투여후 혈청 Total-C치는 309$\pm$46mg/d1에서 201$\pm$37mg/d1로, 281$\pm$41mg/d1에서 218$\pm$31mg/d1로, 혈청LDL-C치는 230$\pm$46mg/d1에서 125$\pm$40mg/d1로, 199$\pm$46mg/d1에서 137$\pm$37mg/d1로 각각 유의하게 감소 하였다. (p < 0.005)혈청 Apo B치는 183$\pm$32mg/d1에서 114$\pm$26mg/d1로, 164$\pm$38mg/d1에서 123$\pm$20mg/d1로, 혈청 Apo B / Apo A-1 ratio는 1.6$\pm$0.4에서 1.0$\pm$0.3으로, 1.4$\pm$0.5에서 1.0$\pm$0.3으로 각각 유의하게 감소하였다. (p < 0.005) Lovastatin 및 pravastatin 투여후 임상적으로 의미있는 중상이나 검사상 이상 소견은 관찰되지 않았다.

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Effects of Jowiseungcheung-tang Extract on the Lipid Metabolism, Anti-oxidation and Inflammatory Reflex High Fat Diet Obese Rats (조위승청탕(調胃升淸湯) 추출액이 비만유도 쥐의 지질대사, 항산화계 및 염증반응계에 미치는 영향)

  • Oh, Sung-Won;Kim, Byoung-Woo
    • The Journal of Internal Korean Medicine
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    • v.34 no.1
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    • pp.1-13
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    • 2013
  • Objectives : The purpose of this study was to investigate the effects of Jowiseungcheung-tang (JWSCT) extract on the lipid metabolism, anti-oxidation and inflammatory reflex. Methods : Male Sprague-Dawley rats were fed a high fat diet for 8 weeks and were randomly divided into 4 groups (10 mice in each group): control group, 100 mg/kg JWSCT group, 200 mg/kg JWSCT group, 300 mg/kg JWSCT group. The control group was administered 100 mg/kg of water, but the other three groups were administered 100, 200, 300 mg/kg JWSCT extract for 4 weeks. After 4 weeks, we measured lipid level, thiobarbituric acid reactive substance (TBARS), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), catalase (CAT), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and cytokines in plasma and liver. The gene expression level and the ratio of apo-B and apo-E were then investigated by way of reverse transcription -polymerase chain reaction (RT-PCR). Results : In the JWSCT group, compared with the control, free fatty acid, triglyceride, total cholesterol, LDL-cholesterol, TBARS, IL-$1{\beta}$, IL-6 and TNF-${\alpha}$ decreased significantly in plasma and liver. However HDL-cholesterol, IL-10, GSH-Px, SOD and CAT increased. In the JWSCT group, compared with the control, the gene expression level and the ratio of apo-A and apo-E decreased significantly in the RT-PCR analysis. Conclusions : The extract of JWSCT has anti-obesity, anti-inflammatory and anti-oxidant effects.

Cholesterol-lowering Effects of Unripe Black Raspberry Water Extract (복분자 미숙과 물추출물의 콜레스테롤 개선 효과)

  • Choi, Hye Ran;Lee, Su Jung;Lee, Jung-Hyun;Kwon, Ji Wung;Lee, Hee Kwon;Jeong, Jong Tae;Lee, Tae-Bum
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.42 no.12
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    • pp.1899-1907
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    • 2013
  • We investigated the effects of unripe black raspberry water extract (UBR-W) and oxidation-LDL treatment on cholesterol levels. Experiments using an established human hepatocellular carcinoma cell line (HepG2) showed a time-dependent increase in expression of LDL receptor after UBR-W treatment. Expression of LDL receptor-related genes, such as SREBP1 and 2, increased upon UBR-W treatment. However, expression of HDL-related genes was unaffected by UBR-W. HMG-CoA reductase activity was reduced by UBR-W treatment, whereas HMG-CoA mRNA expression significantly increased. In addition, the ApoB/ApoA1 mRNA level, which is a predictor of cardiovascular risk, was reduced in a time-dependent manner by UBR-W treatment. Macrophage-like cells (RAW 264.7) showed increased expression of ox-LDL-related genes, such as CD36, scavenger receptor-A, adipophilin, and PPAR-gamma, upon ox-LDL treatment compared to untreated control cells, and quantitative lipid analysis indicated a dramatic increase in lipid accumulation. However, UBR-W treatment significantly reduced expression of ox-LDL-related genes and largely prevented lipid accumulation. The results indicate that UBR-W mediates a cholesterol-lowering effect via inhibition of cholesterol synthesis and induction of LDL uptake through SREBP.