• Title, Summary, Keyword: ApoB mRNA

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Curcumin modulates the apolipoprotein B mRNA editing by coordinating the expression of cytidine deamination to uridine editosome components in primary mouse hepatocytes

  • He, Pan;Tian, Nan
    • The Korean Journal of Physiology and Pharmacology
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    • v.23 no.3
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    • pp.181-189
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    • 2019
  • Curcumin, an active ingredient of Curcuma longa L., can reduce the concentration of low-density lipoproteins in plasma, in different ways. We had first reported that curcumin exhibits hypocholesterolemic properties by improving the apolipoprotein B (apoB) mRNA editing in primary rat hepatocytes. However, the role of curcumin in the regulation of apoB mRNA editing is not clear. Thus, we investigated the effect of curcumin on the expression of multiple editing components of apoB mRNA cytidine deamination to uridine (C-to-U) editosome. Our results demonstrated that treatment with $50{\mu}M$ curcumin markedly increased the amount of edited apoB mRNA in primary mouse hepatocytes from 5.13%-8.05% to 27.63%-35.61%, and significantly elevated the levels of the core components apoB editing catalytic polypeptide-1 (APOBEC-1), apobec-1 complementation factor (ACF), and RNA-binding-motif-protein-47 (RBM47), as well as suppressed the level of the inhibitory component glycine-arginine-tyrosine-rich RNA binding protein. Moreover, the increased apoB RNA editing by $50{\mu}M$ curcumin was significantly reduced by siRNA-mediated APOBEC-1, ACF, and RBM47 knockdown. These findings suggest that curcumin modulates apoB mRNA editing by coordinating the multiple editing components of the edito-some in primary hepatocytes. Our data provided evidence for curcumin to be used therapeutically to prevent atherosclerosis.

Daidzein Modulations of Apolipoprotein B and Fatty Acid Synthase mRNA Expression in Chick Liver Vary Depending on Dietary Protein Levels

  • Choi, Jinho;Song, Jungmin;Choi, Yeon-Mi;Jang, Dong-Ju;Kim, Eunmi;Kim, Inho;Chee, Kew-Mahn
    • Asian-Australasian Journal of Animal Sciences
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    • v.19 no.2
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    • pp.236-244
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    • 2006
  • This study was designed to determine the effects of daidzein (DE) on hepatic lipid metabolism in chicks fed with low protein (LP) diet based on casein. In experiment 1, the male chicks were fed with one of the three levels of dietary protein containing 10.95%, 21.9% and 43.8% protein content for 2 days. In experiment 2, the chicks were fed one of the three levels of protein with or without DE at 1,000 mg/kg diet for 2 days. Experiment 3 was conducted to compare DE (LP+DE) with estradiol (LP+E2) in chicks fed with LP diet for 7 days. Plasma lipid profiles, hepatic lipid profiles, activities of hepatic malic enzyme and isocitrate dehydrogenase (ICDH) were measured. Transcriptions of hepatic fatty acid synthase, apolipoprotein-B (APO-B), and fructose bisphosphatase mRNA were measured by RT-PCR. Increasing dietary protein levels markedly decreased the concentrations of plasma triglycerides, hepatic total lipids, hepatic TG, and the mRNA transcriptions while the increased dietary protein levels increased hepatic ICDH activities in experiment 1. In experiment 2, the effects of dietary protein levels on blood and hepatic lipid content were more prominent than those of the additional DE. Interestingly, plasma TG levels were affected by DE supplementation (p<0.05). In experiment 3, DE inhibited APO-B mRNA expressions and stimulated the accumulation of lipid in the liver through mechanisms different from E2. In this study, we demonstrate that DE has beneficial effects on blood lipid profiles, but that it inhibits APO-B mRNA transcription and aggravates the fatty liver induced by LP diet in chicks.

Korean pine nut oil replacement decreases intestinal lipid uptake while improves hepatic lipid metabolism in mice

  • Zhu, Shuang;Park, Soyoung;Lim, Yeseo;Shin, Sunhye;Han, Sung Nim
    • Nutrition Research and Practice
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    • v.10 no.5
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    • pp.477-486
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    • 2016
  • BACKGROUND/OBJECTIVES: Consumption of pine nut oil (PNO) was shown to reduce weight gain and attenuate hepatic steatosis in mice fed a high-fat diet (HFD). The aim of this study was to examine the effects of PNO on both intestinal and hepatic lipid metabolism in mice fed control or HFD. MATERIALS/METHODS: Five-week-old C57BL/6 mice were fed control diets containing 10% energy fat from either Soybean Oil (SBO) or PNO, or HFD containing 15% energy fat from lard and 30% energy fat from SBO or PNO for 12 weeks. Expression of genes related to intestinal fatty acid (FA) uptake and channeling (Cd36, Fatp4, Acsl5, Acbp), intestinal chylomicron synthesis (Mtp, ApoB48, ApoA4), hepatic lipid uptake and channeling (Lrp1, Fatp5, Acsl1, Acbp), hepatic triacylglycerol (TAG) lipolysis and FA oxidation (Atgl, Cpt1a, Acadl, Ehhadh, Acaa1), as well as very low-density lipoprotein (VLDL) assembly (ApoB100) were determined by real-time PCR. RESULTS: In intestine, significantly lower Cd36 mRNA expression (P<0.05) and a tendency of lower ApoA4 mRNA levels (P = 0.07) was observed in PNO-fed mice, indicating that PNO consumption may decrease intestinal FA uptake and chylomicron assembly. PNO consumption tended to result in higher hepatic mRNA levels of Atgl (P = 0.08) and Cpt1a (P = 0.05). Significantly higher hepatic mRNA levels of Acadl and ApoB100 were detected in mice fed PNO diet (P<0.05). These results suggest that PNO could increase hepatic TAG metabolism; mitochondrial fatty acid oxidation and VLDL assembly. CONCLUSIONS: PNO replacement in the diet might function in prevention of excessive lipid uptake by intestine and improve hepatic lipid metabolism in both control diet and HFD fed mice.

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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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.

Silencing MR-1 attenuates atherosclerosis in ApoE-/- mice induced by angiotensin II through FAK-Akt -mTOR-NF-kappaB signaling pathway

  • Chen, Yixi;Cao, Jianping;Zhao, Qihui;Luo, Haiyong;Wang, Yiguang;Dai, Wenjian
    • The Korean Journal of Physiology and Pharmacology
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    • v.22 no.2
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    • pp.127-134
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    • 2018
  • Myofibrillogenesis regulator-1 (MR-1) is a novel protein involved in cellular proliferation, migration, inflammatory reaction and signal transduction. However, little information is available on the relationship between MR-1 expression and the progression of atherosclerosis. Here we report atheroprotective effects of silencing MR-1 in a model of Ang II-accelerated atherosclerosis, characterized by suppression focal adhesion kinase (FAK) and nuclear factor kappaB ($NF-{\kappa}B$) signaling pathway, and atherosclerotic lesion macrophage content. In this model, administration of the siRNA-MR-1 substantially attenuated Ang II-accelerated atherosclerosis with stabilization of atherosclerotic plaques and inhibited FAK, Akt, mammalian target of rapamycin (mTOR) and NF-kB activation, which was associated with suppression of inflammatory factor and atherogenic gene expression in the artery. In vitro studies demonstrated similar changes in Ang II-treated vascular smooth muscle cells (VSMCs) and macrophages: siRNA-MR-1 inhibited the expression levels of proinflammatory factor. These studies uncover crucial proinflammatory mechanisms of Ang II and highlight actions of silencing MR-1 to inhibit Ang II signaling, which is atheroprotective.

Nutritional and Hormonal Induction of Fatty Liver Syndrome and Effects of Dietary Lipotropic Factors in Egg-type Male Chicks

  • Choi, Y.I.;Ahn, H.J.;Lee, B.K.;Oh, S.T.;An, B.K.;Kang, C.W.
    • Asian-Australasian Journal of Animal Sciences
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    • v.25 no.8
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    • pp.1145-1152
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    • 2012
  • This experiment was conducted with male chicks to investigate the influence of hormones and nutrients on the development of fatty liver syndrome (FLS) as well as the effects of dietary lipotropic factors on hepatic fat accumulation and lipogenic enzyme gene expression. A total of two-hundred sixteen 4-wk-old Hy-Line male chicks were divided into six groups and fed an experimental diet (T1, low-energy diet with low levels of lipotropic factors; T2, high-energy diet with low levels of lipotropic factors; T3 and T5, low-energy diet with high levels of lipotropic factors; T4 and T6, high-energy diet with high levels of lipotropic factors) for six weeks. The chicks in T5 and T6 groups were treated with intramuscular injections of estradiol benzoate for three days prior to biopsy and clinical analysis of FLS. Chicks treated with estrogen had significantly greater liver weights than untreated chicks. The abdominal fat contents were increased in chicks consuming high-energy diets as compared to those consuming low-energy diets. Treatment with estrogen significantly increased the concentrations of serum cholesterol, triacylglycerol and phospholipid (p<0.05). The hepatic triacylglycerol levels were tenfold higher in the estrogen treated chicks than in the untreated chicks. There were no significant differences in malondialdehyde levels between the treatment groups. Estrogen treatment dramatically increased the levels of fatty acid synthetase, acetyl-CoA carboxylase and ApoB mRNA. The results indicated that treatment with exogenous estrogen in growing male chicks induced hepatic fat accumulation, which might be partially due to increased lipogenic enzyme gene expression.

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.

The Expression of Genes Related to Egg Production in the Liver of Taiwan Country Chickens

  • Ding, S.T.;Ko, Y.H.;Ou, B.R.;Wang, P.H.;Chen, C.L.;Huang, M.C.;Lee, Y.P.;Lin, E.C.;Chen, C.F.;Lin, H.W.;Cheng, Winston Teng Kuei
    • Asian-Australasian Journal of Animal Sciences
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    • v.21 no.1
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    • pp.19-24
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    • 2008
  • The purpose of this study was to detect expression of genes related to egg production in Taiwan Country chickens by suppression subtractive hybridization. Liver samples of mRNA extraction from two Taiwan Country chicken strains (L2 and B), originated from the same population but with very distinct egg production rates after long-term selection for egg and meat production respectively. Two-way subtraction was performed. The hepatic cDNA from the low egg production chickens (B) was subtracted from the hepatic cDNA from the high egg production strain (L2). The reversed subtraction (L2 from B) was also performed. The resulting differentially expressed gene fragments were cloned and sequenced. We sequenced 288 clones from the forward subtraction and 96 clones from the reverse subtraction. These genes were subjected to further screening to confirm the differential expression between the two genetic breeds of chickens. The apolipoprotein B (apoB) was expressed to a greater extent in the liver of the L2 than in the B line chickens. The 5-aminoimidazole- 4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (PURH) was expressed to a greater extent in the liver of the B than in the L2 strain chickens. We demonstrated that both apoB and PURH were more highly expressed in the liver than that in other tissues (muscle, ovary, and oviduct) in laying Taiwan Country chickens. Taken together, these data suggest that after the selection for egg production, expression of apoB and PURH genes were also changed. Whether the changed expression of these genes is directly related to egg production is not known, but these two genes may be useful markers for egg laying performance in Taiwan Country chickens.