• Title/Summary/Keyword: High density lipoproteins(HDL)

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Different Functional and Structural Characteristics between ApoA-I and ApoA-4 in Lipid-Free and Reconstituted HDL State: ApoA-4 Showed Less Anti-Atherogenic Activity

  • Yoo, Jeong-Ah;Lee, Eun-Young;Park, Ji Yoon;Lee, Seung-Taek;Ham, Sihyun;Cho, Kyung-Hyun
    • Molecules and Cells
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    • v.38 no.6
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    • pp.573-579
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    • 2015
  • Apolipoprotein A-I and A-IV are protein constituents of high-density lipoproteins although their functional difference in lipoprotein metabolism is still unclear. To compare anti-atherogenic properties between apoA-I and apoA-4, we characterized both proteins in lipid-free and lipidbound state. In lipid-free state, apoA4 showed two distinct bands, around 78 and $67{\AA}$ on native gel electrophoresis, while apoA-I showed scattered band pattern less than $71{\AA}$. In reconstituted HDL (rHDL) state, apoA-4 showed three major bands around $101{\AA}$ and $113{\AA}$, while apoA-I-rHDL showed almost single band around $98{\AA}$ size. Lipid-free apoA-I showed 2.9-fold higher phospholipid binding ability than apoA-4. In lipid-free state, $BS_3$-crosslinking revealed that apoA-4 showed less multimerization tendency upto dimer, while apoA-I showed pentamerization. In rHDL state (95:1), apoA-4 was existed as dimer as like as apoA-I. With higher phospholipid content (255:1), five apoA-I and three apoA-4 were required to the bigger rHDL formation. Regardless of particle size, apoA-I-rHDL showed superior LCAT activation ability than apoA-4-rHDL. Uptake of acetylated LDL was inhibited by apoA-I in both lipid-free and lipid-bound state, while apoA-4 inhibited it only lipid-free state. ApoA-4 showed less anti-atherogenic activity with more sensitivity to glycation. In conclusion, apoA-4 showed inferior physiological functions in lipid-bound state, compared with those of apoA-I, to induce more pro-atherosclerotic properties.

Suberitenone B: A Novel Inhibitor of Cholesteryl Ester Transfer Protein (CETP) with an Unprecedented Skeletal Class from the Antarctic Sponge Suberites sp.

  • Shin, Jongheon;Seo, Youngwan;Rho, Jung-Rae;Baek, Eunjoo;Kwon, Byoung-Mog;Jeong, Tae-Sook;Bok, Song-Hae
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1995.04a
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    • pp.64-64
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    • 1995
  • Cholesteryl Ester Transfer Protein (CETP) mediates the transfer of cholesterol ester and triglyceride between high-density lipoprotein (HDL) and other low-density lipoproteins, therefore, it might influence HDL levels. The levels of HDL is closely related to the atherogenic diseases in human and there were several reports that the trasgenic mice expressing CETP had much worse atherosclerosis than non-expressing control one. Therefore, selective inhibitors of CETP have the potential to be used as antiatherosclerotic agents. Continued screening for potent inhibitors of CETP led to the isolation of Suberitenone B from marine sponge. Suberitenone B, sesterterpenoids of a new skeletal class have been isolated from the sponge Suberites sp. collected from King George Island the Antartic. The structure of the metabolite has been determined by NMR experiments and chemical methods.

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Effects of the Particulate Matter2.5 (PM2.5) on Lipoprotein Metabolism, Uptake and Degradation, and Embryo Toxicity

  • Kim, Jae-Yong;Lee, Eun-Young;Choi, Inho;Kim, Jihoe;Cho, Kyung-Hyun
    • Molecules and Cells
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    • v.38 no.12
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    • pp.1096-1104
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    • 2015
  • Particulate $matter_{2.5}$ ($PM_{2.5}$) is notorious for its strong toxic effects on the cardiovascular, skin, nervous, and reproduction systems. However, the molecular mechanism by which $PM_{2.5}$ aggravates disease progression is poorly understood, especially in a water-soluble state. In the current study, we investigated the putative physiological effects of aqueous $PM_{2.5}$ solution on lipoprotein metabolism. Collected $PM_{2.5}$ from Seoul, Korea was dissolved in water, and the water extract (final 3 and 30 ppm) was treated to human serum lipoproteins, macrophages, and dermal cells. $PM_{2.5}$ extract resulted in degradation and aggregation of high-density lipoprotein (HDL) as well as low-density lipoprotein (LDL); apoA-I in HDL aggregated and apo-B in LDL disappeared. $PM_{2.5}$ treatment (final 30 ppm) also induced cellular uptake of oxidized LDL (oxLDL) into macrophages, especially in the presence of fructose (final 50 mM). Uptake of oxLDL along with production of reactive oxygen species was accelerated by $PM_{2.5}$ solution in a dose-dependent manner. Further, $PM_{2.5}$ solution caused cellular senescence in human dermal fibroblast cells. Microinjection of $PM_{2.5}$ solution into zebrafish embryos induced severe mortality accompanied by impairment of skeletal development. In conclusion, water extract of $PM_{2.5}$ induced oxidative stress as a precursor to cardiovascular toxicity, skin cell senescence, and embryonic toxicity via aggregation and proteolytic degradation of serum lipoproteins.

F1064m: New Inhibitor of Cholesteryl Ester Transfer Protein (CETP), Isolated from Gliocladium virens F1064

  • Kwon, Byoung-Mog;Cho, Joung-Suk;Jeong, Tae-Sook;Kim, Sung-Uk;Son, Kwang-Hee;Kim, Young-Kook;Nam, Ji-Youn;Han, Kyu-Hoon;Bok, Song-Hae
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1995.04a
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    • pp.65-65
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    • 1995
  • Cholesteryl Ester Transfer Protein(CETP), a hydrophobic glycoprotein with molecular mass 74KDa, is a lipid transfer protein found in plasma which mediates the transfer of cholesterol ester and triglyceride between high-density lipoprotein (HDL) and other lipoproteins, therefore, it might influence HDL levels. The lipoprotein profile associated with human CETP deficiency (that are two Japanese families, high HDL and low LDL) has low atherogenic potential, raising the possibility that CETP inhibitors can be used as antiatherosclerotic drugs.

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Effects of a Health Promotion Program on College Students Who are on the Brink of Dyslipidemia, Based on Cox's Interaction Model (Cox의 상호작용 모델에 근거한 이상지질혈증 경계범위 대학생의 건강증진 프로그램 효과)

  • Lee, Hye-Kyung;Park, Yeon-Suk
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.15 no.5
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    • pp.3058-3068
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    • 2014
  • This experimental research is aimed to apply a health promotion program based on Cox's interaction model to such college students as are on the brink of dyslipidemia, so as to investigate the effects of the program on the subjects' blood lipid indexes including total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), and low-density lipoproteins (LDL). The subjects are 39 in all including the experimental group comprising 20 and the control group comprising 19. The analyses applied include descriptive statistics using SPSS WIN 18.0, $X^2$-test, independent t-test, and paired t-test. By means of nursing interventions which are an element of client-professional interaction, the following were offered including health information (exercise management, dietary management, health education), emotional support (sharing of experiences, encouragement, self expression), decision-making controlling (counselling by phone), and professional/ technical abilities; and blood lipid indexes were measured before and after the interventions. The results of this research found that TC, TG and LDL decreased significantly and HDL increased significantly in the experimental group, which indicates that the health promotion program was effective.

Solution Structure of pA2, the Mimotopic Peptide of Apolipoprotein A-I, by NMR Spectroscopy

  • Won, Ho-Shik
    • Bulletin of the Korean Chemical Society
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    • v.32 no.11
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    • pp.4016-4020
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    • 2011
  • A number of mimetic peptides of apolipoprotein A-I, a major component for high density lipoproteins (HDL), were screened from the phase-displayed random peptide library by utilizing monoclonal antibodies (A12). A mimetic peptide for A12 epitope against apolipoprotein A-I was selected as FVLVRDTFPSSVCCP(pA2) exhibiting 45% homology with Apo A-I in the BLAST search. Solution structure determination of this mimotope was made by using 2D-NMR data and NMR-based distance geometry (DG)/molecular dynamic calculations. The resulting DG structures had low penalty value of 0.4-0.6 ${\AA}^2$ and the total RMSD of 0.7-1.7 ${\AA}$. The mimotope pA2 exhibited a characteristic ${\beta}$-turn conformation from Val[2] to Phe[8] near Pro[9] residue.

Solution State Structure of pA1, the Mimotopic Peptide of Apolipoprotein A-I, by NMR Spectroscopy

  • Kim, Hyo-Joon;Won, Ho-Shik
    • Bulletin of the Korean Chemical Society
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    • v.32 no.9
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    • pp.3425-3428
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    • 2011
  • Apolipoprotein A-I (Apo A-I) is a major component for high density lipoproteins (HDL). A number of mimetic peptides of Apo A-I were screened from the phase-displayed random peptide library by utilizing monoclonal antibodies (A12). Mimetic peptide for A12 epitope against Apo A-I was selected as CPFARLPVEHHDVVGL (pA1). From the BLAST search, the mimetic peptide pA1 had 40% homology with Apo A-I. As a result of the structural determination of this mimotope using homo/hetero nuclear 2D-NMR techniques and NMR-based distance geometry (DG)/molecular dynamic (MD) computations, DG structure had low penalty value of 0.3-0.7 ${\AA}^2$ and the total RMSD was 0.6-1.6 ${\AA}$. The mimotope pA1 exhibited characteristic conformation including a ${\beta}$-turn from Pro[7] to His[11].

Functional Properties of Enzymatically Modified Egg Yolk Powder Produced by Phospholipase $A_2$ Treatment

  • Kim, Mi-Ra;Shim, Jae-Yong;Park, Ki-Hwan;Imm, Jee-Young
    • Food Science and Biotechnology
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    • v.17 no.6
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    • pp.1289-1293
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    • 2008
  • Fresh egg yolk (EY) was enzymatically modified using phospholipase $A_2$ ($PLA_2$) to produce an enzymatically modified-egg yolk powder (EM-EYP). The EM-EYP offered significantly higher emulsifying activity, emulsion stability, protein solubility, and mayonnaise stability than the control EYP. By employing $PLA_2$ in the enzymatic modification process, structural changes occurred in the phospholipids and lipoproteins of the yolk, and cleavage of apo-high density lipoprotein (HDL) components (Mw 105 kDa) was detected by sodium dodecyl sulfate-polyaerylamide gel electrophoresis (SDS-PAGE). Based on its functional properties, EM-EYP has great potential as a replacement for fresh EY in the production of processed food products such as mayonnaise.

The Effects of Docking on Growth Traits, Carcass Characteristics and Blood Biochemical Parameters of Sanjabi Fat-tailed Lambs

  • Nooriyan Sarvar, E.;Moeini, M.M.;Poyanmehr, M.;Mikaeli, E.
    • Asian-Australasian Journal of Animal Sciences
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    • v.22 no.6
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    • pp.796-802
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    • 2009
  • The effects of docking on growth traits, fattening performance, carcass characteristics and blood biochemical parameters were investigated using 24 fat-tailed Sanjabi single-born male lambs raised from a large commercial sheep herd. The lambs were randomly divided into two groups. One group (n = 12) were docked at two days of age with rubber-rings using an elastrator. The second group (n = 12) were left intact. After weaning (90 days), all lambs were moved to rustic rangelands for 40 days. Then all the lambs were fed concentrates ad libitum for 60 days during the fattening period. Growth traits, body weight and average daily gain (kg) were recorded at the end of the weaning and fattening periods. Blood biochemical parameters including urea, total protein, glucose, triglycerides, cholesterol, low-density lipoproteins (LDL) and high-density lipoproteins (HDL) were measured during the fattening period. Finally, at the end of the fattening period, eight lambs (4 intact and 4 docked lambs) were slaughtered in order to determine carcass characteristics. Fat-tail docking had no effect (p>0.05) on lamb growth from birth to weaning. Body weight and average daily gain of docked lambs were significantly higher (p<0.05) than for intact lambs at the end of the fattening period. There was no difference in carcass measurements between the two groups, except for chest depth and leg weight which were higher (p<0.05) in docked lambs. During the fattening period, cholesterol and LDL of docked lambs were less than in intact lambs (p<0.05). The current results indicated that docking with rubber rings causes an improvement in growth traits during the fattening period and leads to desirable carcass characteristics compared to intact lambs; interestingly, this procedure had a significant effect on the lowering of blood cholesterol and LDL of docked lambs.

Inhibitory Effects of Antisense RNA on Expression of Cholesteryl Ester Transfer Protein in Vaccinia Virus Expression System

  • Lee, Myung-Hoon;Jang, Moon-Kyoo;Park, Yong-Bok
    • BMB Reports
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    • v.28 no.3
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    • pp.243-248
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    • 1995
  • Cholesteryl ester transfer protein (CETP), a hydrophobic glycoprotein promoting transfer of cholesteryl esters (CE) from high-density lipoproteins (HDL) to lower-density lipoproteins in the plasma, has been recognized a potent atherogenic factor during the development of coronary artery diseases. This study demonstrated a possible utilization of antisense RNA to inhibit expression of the CETP gene using vaccinia virus as an expression system. The CETP cDNA was inserted into a transfer vector (pSC11) in sense and antisense orientations and used to generate recombinant viruses. Recombinants containing sense or antisense orientations of the CETP cDNA were isolated by $TK^-$ selection and X-gal test. The inserted CETP cDNAs in the recombinants were identified by Southern blot analysis and allowed to transcribe in host cells (CV-1). Expressions of the exogenous CETP mRNA, extracted from the CV-1 cells coinfected with viruses containing sense and antisense DNAs, were monitored by Northern blot analysis using the CETP cDNA probe, by Western blot analysis using monoclonal antibody against the C-terminal active region of the CETP and by the CETP assay. Decreased expressions of the exogenous CETP cDNA were clearly evident in the Northern and Western blot analyses as the dose of antisense expression increased. In the CETP assay, the CETP activities decreased compared to the activity obtained from the cell extracts infected with sense construct only.

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