• Title/Summary/Keyword: Apolipoprotein E (apoE)

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Molecular Cloning of a cDNA Encoding Putative Apolipophorin from the Silkworm, Bombyx mori

  • Yun, Eun-Young;Goo, Tae-Won;Kim, Sung-Wan;Hwang, Jae-Sam;Park, Kwang-Ho;Kwon, O-Yu;Kang, Seok-Woo
    • International Journal of Industrial Entomology and Biomaterials
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    • v.7 no.2
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    • pp.145-149
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    • 2003
  • ApolipophorinIII (apoLp-III) is a protypical exchangeable apolipoprotein that is abundant in hemolymph of many insect species. Its function lies in the stabilization of low-density lipophorin particles (LDLp) crossing the hemocoel in phases of high energy consumption to deliver lipids from the fat body to the flight muscle cells. But, recent studies with naive Galleria mellonella-apoLp-III gave first indication of an unexpected role of that protein in insect immune activation. In this research, we cloned a cDNA encoding putative apoLp-III from the silkworm, Bombyx mori injected with E. coli and characterized its role. We constructed a cDNA library using whole bodies of B. mori larvae injected with E. coli, carried out the differential screening, and selected the up-regulated clones. Among these clones, we focused on a cDNA showing a high sequence similarity to the apolipophorinIII from other insects and analyzed the nucleotide and deduced amino acid sequences. The pupative B. mori Jam123 apoLp-III cDNA contained 1,131 bp encoding 186 amino acid residues. Phylogenetic analysis revealed that the nucleotide and amino acid sequences of the B. mori apoLp-III cDNA formed a highly inclusive subgroup with Bombycidae. But, it was interesting that B. mori Jam123 is closer to B. mandarina than B. mori P50 and B. mori N4. Northern blot analysis showed a signal in the fat body, posterior silkgland and midgut.

ANIMAL AND HUMAN STUDIES ON THE ROLE OF SOYBEAN, RICE AND NUTS CONSUMPTION IN HYPERCHOLESTEROLEMIA AND ATHEROSCLEROSIS

  • Imaizumi Katsumi
    • Proceedings of the Korean Society of Food Science and Nutrition Conference
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    • 2001.12a
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    • pp.61-68
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    • 2001
  • Soybean, rice and nuts are the staple foods in South East Asia. In order to clarify the function of these foods in relation to coronary heart diseases, we have done a series of experiments using animals and humans. Soybean protein preparations (SPI) in comparison with an animal protein, casein (CAS), resulted in reducing atherosclerotic lesion development in apolipoprotein (apo) E deficient mice that develop an advanced lesion similar to that in humans. This action was attributed to the protein, since the ethanol-extracted SPI (EE-SPI), from which isoflavones and saponins removed, lowered the lesion development in apo E-deficient mice. However, The EE-SPI, compared to the SPI, resulted in a decrease of mRNA for key proteins of cholesterol metabolism (low density lipoprotein receptor and cholesterol 7$\alpha$-hydroxylase) in hypercholesterolemic rats, followed by an elevation of the serum cholesterol level, indicating a contribution of isoflavones to the serum cholesterol level. Rice protein (RPI) was also effective to lower the lesion development in apo E deficient mice. Both the SPI and RPI led to an increased level of the serum NOiN03, metabolites of NO. This effect appeared to be attributed to their high content of arginine. Besides, C57BL/6J mice fed a diet containing whole grain rice had an elevation of the serum high-density lipoprotein cholesterol. Furthermore, rice bran oil and the unsaponifiable fraction that is rich in plant sterols were effective to lower serum cholesterol levels in hypercholeserolemic rats. Finally, we tested if walnuts consumption would be hypocholesterolemic for Japanese. A diet containing walnuts effectively lowered the serum total and low density lipoprotein cholesterol in Japanese men and women. These animal and human experiments would be relevant to advocate publics to keep consuming diets including soybean, rice and nuts for their healthful life.

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Gene Therapy for Bovine Fatty Liver : Possibilities and Problems - A Review

  • Chen, Daiwen;Grummer, Ric
    • Asian-Australasian Journal of Animal Sciences
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    • v.14 no.9
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    • pp.1331-1341
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    • 2001
  • Dairy cows are prone to fatty liver during the time of periparturient. Despite of the extensive studies, etiology and solutions for fatty liver are still not well known.The liver synthesizes triglycerides (TG) using precursors from bloodstream and secretes TG in form of very low density lipoprotein (VLDL) into bloodstream for the utilization by peripheral tissues. When the amount of TG synthesis exceeds the amount of secretion in VLDL-TG, TG accumulation within the liver occurs. Hepatic VLDL assembly and secretion involve multi-biochemical events.The availabilities of apolipoprotein B (apoB), E (apoE), microsomal triglyceride transfer protein (MTP) and soluble low density lipoprotein (LDL) receptor are now believed to be some of the main regulators for hepatic VLDL assembly and secretion. Studies in transgenic animals show that overexpression of these proteins stimulates VLDL production and secretion, which provides a possibility for alleviating bovine fatty liver by gene therapy. However, many problems remain to be solved to attain this goal. This review focuses on the molecular mechanisms of hepatic VLDL assembly and secretion, and the possibilities and problems of applying the knowledges to solve bovine fatty liver by gene therapy.

Kisspeptin-10 Enhanced Egg Production in Quails Associated with the Increase of Triglyceride Synthesis in Liver

  • Wu, J.;Fu, W.;Huang, Y.;Ni, Y.;Zhao, R.
    • Asian-Australasian Journal of Animal Sciences
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    • v.26 no.8
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    • pp.1080-1088
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    • 2013
  • Our previous results showed that kisspeptin-10 (Kp-10) injections via intraperitoneal (i.p.) once daily for three weeks notably promoted the egg laying rate in quails. In order to investigate the mechanism behind the effects of Kp-10 on enhancing the egg laying rate in birds, this study focused on the alternations of lipids synthesis in liver after Kp-10 injections. 75 female quails (22 d of age) were allocated to three groups randomly, and subjected to 0 (control, Con), 10 nmol (low dosage, L) and 100 nmol (high dosage, H) Kp-10 injections via i.p. once daily for three weeks, respectively. At d 52, quails were sacrificed and sampled for further analyses. Serum $E_2$ concentration was increased by Kp-10 injections, and reached statistical significance in H group. Serum triglyceride (TG) concentrations were increased by 46.7% in L group and 36.8% in H group, respectively, but did not reach statistical significance, and TG contents in liver were significantly elevated by Kp-10 injections in a dose-dependent manner. Serum total cholesterol (Tch) concentrations significantly decreased in H group, while in H group the hepatic Tch content was markedly increased. The level of non-esterified fatty acid (NEFA), apolipoprotein A1 and B (apoA1 and apoB) were not altered by Kp-10 injections. The genes expression of sterol regulatory element binding protein-1 (SREBP-1), fatty acid synthetase (FAS), apolipoprotein VLDL-II (apoVLDL-II), cholesterol $7{\alpha}$-hydroxylase (CYP7A1) and vitellogenin II (VTG-II) were significantly up-regulated by high but not low dosage of Kp-10 injection compared to the control group. However, the expression of SREBP-2, acetyl-CoA carboxylase ($ACC_{\alpha}$), malic enzyme (ME), stearoyl-CoA (${\Delta}9$) desaturase 1 (SCD1), apolipoprotein A1 (apoA1), fatty acid binding protein 2 (FABP2), 3-hydroxyl-3-methyl glutaryl-coenzyme A reductases (HMGCR), estrogen receptor ${\alpha}$, ${\beta}$($ER{\alpha}$ and ${\beta}$) mRNA were not affected by Kp-10 treatment. In line with hepatic mRNA abundance, hepatic SREBP1 protein content was significantly higher in H group. Although the mRNA expression was not altered, the content of $ER{\alpha}$ protein in liver was also significantly increased in H group. However, SREBP-2 protein content in liver was not changed by Kp-10 treatment. In conclusion, exogenous Kp-10 consecutive injections during juvenile stage significantly advanced the tempo of egg laying in quails, which was associated with the significant elevation in hepatic lipids synthesis and transport.

Molecular imaging of atherosclerosis using reporter gene system

  • Yoo, Ran Ji;Lee, Kyochul;Kang, Joo Hyun;Lee, Yong Jin
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.4 no.1
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    • pp.26-31
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    • 2018
  • Macrophages play a key role in atherosclerotic plaque formation, but their participation has been discerned largely via ex vivo analyses of atherosclerotic lesions. Therefore, we aimed to identify atherosclerosis on noninvasive in vivo imaging using reporter gene system. This study demonstrated that recruitment of macrophages could be detected in atherosclerotic plaques of Apolipoprotein E knockout (ApoE-/-) mice with a sodium iodide symporter (NIS) gene imaging system using $^{99m}Tc-SPECT$. This novel approach to tracking macrophages to atherosclerotic plaques in vivo could have applications in studies of arteriosclerotic vascular disease.

Root bark extract of Cudrania tricuspidata reduces LPS-induced inflammation in macrophages of atherogenic mice

  • Lee, Mi-Ran
    • Journal of the Korea Society of Computer and Information
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    • v.25 no.10
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    • pp.115-123
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    • 2020
  • In this paper, we propose to evaluate the potential anti-inflammatory properties of root bark extract of Cudrania (C.) tricuspidata on lipopolysaccharide (LPS)-induced inflammation in macrophages of apolipoprotein E (ApoE) knockout (ApoE-/-) mice, murine model of atherosclerosis. Atherosclerosis is a chronic vascular inflammatory disease. C. tricuspidata is a small tree of the Moraceae family and its extract has anti-inflammatory activities. However, its role in the progress of atherosclerosis is not yet clear. To determine anti-inflammatory effects of C. tricuspidata in atherogenesis, we applied LPS in peritoneal macrophages of ApoE-/- mice and measured cell viability by CCK-8 and expression of pro-inflammatory cytokines by qRT-PCR following treatment with root bark extract of C. tricuspidata. Research data was expressed as differences between the cells treated with LPS and root bark extract and the cells treated with LPS alone (control) by a two-tailed non-parametric Mann-Whitney U-test using GraphPad Instat program. No cytotoxic effect was observed when the cells were treated with the extract at concentrations ≤ 100 ㎍/mL. The expression of inflammatory cytokines, including MCP-1, IL-1β, IFN-γ, TNF-α, and IL-6 were inhibited by the extract. These results indicated that the extract has an anti-inflammatory effect and therefore a possible role in the treatment of atherosclerosis.

The Hypocholesterolemic Effects of Soymilk Fermented with Bacillus subtilis Compared to Soymilk with Cheonggukjang Powder in Apolipoprotein E Knockout Mice

  • Seo, Kyoung-Chun;Kim, Mi-Jin;Hong, Sun-Hee;Cha, So-Yeon;Noh, Jeong-Sook;Kim, Mi-Jeong;Song, Yeong-Ok
    • Preventive Nutrition and Food Science
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    • v.15 no.2
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    • pp.83-87
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    • 2010
  • The cholesterol-lowering effects of soymilk fermented with Bacillus subtilis KCCM42923 were studied in apolipoprotein E knockout (ApoE KO) mice and compared to the cholesterol-lowering effects of soymilk to which cheonggukjang powder had been added. ApoE KO mice were divided into 3 groups (n=7/group). Animals were fed either an atherogenic diet only (AD, control group), an AD supplemented with fermented soymilk containing Corni fructus (FSM group), or an AD supplemented with soymik to which cheonggukjang (CGJ) powder had been added at 5% (w/v) (CPS group) for 8 weeks. The amount of FSM or CPS supplementing the AD was 20.8 mL/kg BW. There were no differences in either body weight gain or organ weights among three groups. In the FSM group, the concentration of plasma total cholesterol (TC) and LDL cholesterol (LDLC) were significantly decreased by 26.2% and 30.3% compared with the values of the control group (p<0.05). However, the triglyceride (TG) and HDL-cholesterol (HDLC) levels were not affected. These beneficial effects of FSM on suppressing the increase in plasma cholesterol level by AD were greater than those of CPS, which revealed 15.4% and 16.4% inhibition for TC and LDLC, respectively. However, these differences between FSM and CPS groups were not significantly different. A preventative effect of FSM or CPS on the accumulation of hepatic TC, but not on TG, was observed. FSM and CPS did not demonstrate any effects on fecal lipid excretion. In conclusion, the cholesterol-lowering effects of the soymilk fermented with Bacillus subtilis KCCM42923 were comparable to CGJ powder-added soymilk. These results suggest that drinking FSM might provide beneficial effects on controlling plasma cholesterol levels.

Extract of high hydrostatic pressure-treated danshen (Salvia miltiorrhiza) ameliorates atherosclerosis via autophagy induction

  • Ko, Minjeong;Oh, Goo Taeg;Park, Jiyong;Kwon, Ho Jeong
    • BMB Reports
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    • v.53 no.12
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    • pp.652-657
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    • 2020
  • Danshen (Salvia miltiorrhiza) is a traditional medicinal plant widely used in Asian countries for its pharmacological activities (e.g., amelioration of cardiovascular diseases). In this study, we investigated the anti-atherosclerotic activity of raw danshen root extract prepared using high hydrostatic pressure (HHP) at 550 MPa for 5 min and hot water extraction. This method was useful for elimination of bacteria from cultured danshen plants and for better extraction yield of active principles. The HHP-treated danshen extract (HDE) inhibited proliferation of human umbilical vein endothelial cells (HUVECs) and induced autophagy that was assessed by LC3 conversion and p62 degradation. HDE suppressed foam cell formation in oxLDL-induced RAW264.7 macrophages; lysosomal activity simultaneously increased, measured by acridine orange staining. HDE also reduced atherosclerotic plaque development in vivo in apolipoprotein E knock-out (ApoE-/-) mice fed a high cholesterol diet. Taken together, these results indicated that HDE exhibited anti-atherosclerotic activity via autophagy induction.

Carbon Nanotubes Multi Electrodes Array to Image Capacitance for Label-free Discrimination of Lipid Region in Atherosclerosis ex vivo

  • Song, Jun-Ho;Lee, Seon-Mi;Han, Nal-Ae;Yu, Gyeong-Hwa
    • Proceedings of the Korean Vacuum Society Conference
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    • 2016.02a
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    • pp.372.1-372.1
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    • 2016
  • Recently, there are a lot of diseases all around the world. Out of them, Atherosclerosis (AS) is the most common cause of stroke, cardiovascular mortality, and myocardial infarction. The macrophage-derived foam cell, which is formed by oxidized low-density lipoprotein (oxLDL), is the crucial marker for AS. In this study, we report a label-free capacitance imaging technique with multi-electrode array (MEA). The lipid-rich aorta arch lesions, which are derived from an apolipoprotein-E receptor-deficient (apoE-/-) mouse, exhibit higher capacitance than the lipid-free aorta arch, allowing the capacitance imaging of lipid region in atherosclerosis. To improve the contacts between MEA and tissue, polypyrrole(PPy)-coated multi walled carbon nanotubes (MWNTs) multi electrode array (PPy-MWNTs-MEA) was fabricated. Compared to TiN-MEA, PPy-MWNTs-MEA yielded lower contact impedance and better capacitance images. In addition, we have also developed a flexible MEA using single walled carbon nanotubes on a PET substrate. The lipid region could be discriminated in the capacitance images of the lipid-rich aorta arch lesions measured using flexible MEA, demonstrating a feasibility of in vivo applications.

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Induced Mutant Animal Models for Studying the Genetics of Hypertension and Atherosclerosis

  • Oh, Goo-Taeg
    • Toxicological Research
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    • v.17
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    • pp.289-292
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    • 2001
  • Gene targeting allows precise, predetermined changes to be made in a chosen gene in the mouse genome. To date, targeting has been used most often for generation of animals completely lacking the product of a gene of interest. Models of essential hypertension have been produced by mutated genes relating renin angiotensin system. The most significant contribution to understanding the genetic etiology of essential hypertension is probably the demonstration that discrete alterations in the expression of a variety of different genes can individually cause changes in the blood pressures of mice, even when the mice have all their compensatory mechanisms intact. These effects are readily detected in animals having moderate decreases in gene function due to heterozygosity for gene disruptions or modest increases due to gene duplication. As a species the mouse is highly resistant to atherosclerosis. However. through induced mutations it has been possible to develop lines oj mice that are deficient in apolipoprotein E, a ligand important in lipoprotein clearance, develop atherosclerotic lesions resembling those observed in humans. The atherosclerotic lesions in apoE-deficient mice have been well characterized, and they resemble human lesions in their sites of predilection and progression to the fibroproliferative stage. Other promising models are mice that are deficient in the low-density lipoprotein receptor. Considerable work still remains to be done in dissecting out in a rigorous manner the effects of alterations in single genes on the induction or progression of atherosclerosis and on the control of blood pressures. Perhaps even more exciting is the opportunity now becoming available to breed animals in which the effects oj precise differences in more than one gene can be studied in combination.

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