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      KCI등재 SCIE SCOPUS

      Ginsenoside Rb2 Upregulates the Low Density Lipoprotein Receptor Gene Expression through the Activation of the Sterol Regulated Element Binding Protein Maturation in HepG2 Cells

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      https://www.riss.kr/link?id=A75963064

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      다국어 초록 (Multilingual Abstract)

      Ginsenosides, a group of Panax ginseng saponins, exert the lowering effects of plasma cholesterol levels in animals. We had reported earlier that ginsenoside Rb2 upregulate low-density lipoprotein receptor (LDLR) expression via a mechanism that is dep...

      Ginsenosides, a group of Panax ginseng saponins, exert the lowering effects of plasma cholesterol levels in animals. We had reported earlier that ginsenoside Rb2 upregulate low-density lipoprotein receptor (LDLR) expression via a mechanism that is dependent of the activation of sterol response element binding protein 2 (SREBP-2) expression. This study was conducted to determine the effects of ginsenoside Rb2 on the expression of the hepatic LDLR expression at cellular levels using HepG2 cells, and to evaluate whether the sterol response element binding protein 1 (SREBP-1) was involved in the regulation of LDLR expression. Incubation of HepG2 cells in serum-free medium supplemented with cholesterol (10 μg/ml) for 8 hours decreased the mRNAs of LDLR mRNA by 12% and SREBP-1 mRNA by 35%. Ginsenoside Rb2 antagonized the repressive effects of cholesterol and increased both LDLR and SREBP-1 mRNA expression to 1.5- and 2-fold, respectively. Furthermore, Western blot and confocal microscopic analyses with SREBP-1 polyclonal antibody revealed that ginsenoside Rb2 enhanced the maturation of the SREBP-1 from the inactive precursor form in ER membrane to the active transcription factor form in nucleus. These results suggest that ginsenoside Rb2 upregulates LDLR expression via a mechanism that is dependent of the activation of not only SREBP-2 expression, but also SREBP-1 expression and maturation, and also indicate that the pharmacological value of ginsenoside Rb2 may be distinguished from that of lovastatin which is reported that it upregulate LDLR through SREBP-2 only, not through SREBP-1.

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      목차 (Table of Contents)

      • Abstract
      • INTRODUCTION
      • MATERIALS AND METHODS
      • RESULTS
      • DISCUSSION
      • Abstract
      • INTRODUCTION
      • MATERIALS AND METHODS
      • RESULTS
      • DISCUSSION
      • ACKNOWLEDGEMENT
      • REFERENCES
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      참고문헌 (Reference)

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      1 "transcriptional regulators of lipid synthetic genes.Prog Lipid Res. 40" 40 : 439-452, 2001

      2 "reg-ulation of cholesterol metabolism by proteolysis of a mem-brane-bound transcription factor. Cell. 89" 89 : 331-340, 1997

      3 "abasic-helix-loop-helix-leucine zipper protein that controlstranscription of the low density lipoprotein receptor gene.Cell. 75" -1, 187-1971993

      4 "a second basic-helix-loop-helix-leucine zipper protein that stimulates tran-scription by binding to a sterol regulatory element. Proc NatlAcad Sci USA. 90" 11603-2 11607, 1993

      5 "The pharmacological treat-ment of dyslipidemia. Annu Rev Pharmacol Toxicol. 29" C.A. and Harris 265-288, 1989

      6 "The mechanism of LDL receptor up-regulation by gin-senoside Rb2 in HepG2 cultured under enriched cholesterolcondition. J. Ginseng Res. 28" 28 (28): 87-93, 2004

      7 "Single-step method ofRNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 162" 156-159, 1987

      8 "S.Y. Preventive efect of ginseng intakeagainst various human cancers a case-control study on 1987pairs. Cancer Epidemiol Biomarkers Prev. 4" 4 : 401-408, 1995

      9 "S.N. Geneexpression of sterol regulatory element-binding proteins inhamster small intestine. J Lipid Res. 42" 42 : 1-8, 2001

      10 "Role of ginsenosides as bioreactor in lipid metab-olism. J Nutr Sci Vitaminol" 298-301, 1992

      11 "Regulationof plasma cholesterol by lipoprotein receptors. Science. 212" 628-635, 1981

      12 "Regulation of intracellular choles-Vol. 29 Ginsenoside Rb2 Upregulates the LDLR Expression through the Activation of the SREBP Maturation 165terol metabolism. Cell Struct Funct. 20" 20 : 421-427, 1995

      13 "Regu-lated cleavage of sterol regulatory element binding proteinsrequires sequences on both sides of the endoplasmic reticu-lum membrane. J Biol Chem. 271" 271 : 10379-10384, 1996

      14 "Pharmacologic consequences of cholesterol absorptioninhibition alteration in cholesterol metabolism and reductionin plasma cholesterol concentration induced by the syntheticsaponin beta-tigogenin cellobioside" mali (mali): 377-88818 395, 1993

      15 "Nuclearimport of sterol regulatory element-binding protein-2"

      16 "Non-organ specific cancer preven-tion of ginseng a prospective study in Korea. Int J Epide-miol. 27" 27 : 359-364, 1998

      17 "M.S.Identification of nucleotides responsible for enhancer activ-ity of sterol regulatory element in low density lipoproteinreceptor gene. J Biol Chem. 265" 2306-2310, 1990

      18 "Invivo antimetastatic action of ginseng protopanaxadiol saponinsis based on their intestinal bacterial metabolites after oraladministration. Oncol Res. 9" 9 : 411-417, 1997

      19 "Identification of complexes between theCOOH-terminal domains of sterol regulatory element-bind-ing proteins" 272 : 20213-20221, 1997

      20 "Hyperlipemia-improving effects of ginsenoside-Rb2 in strepto-zotocin-diabetic rats. Chem Pharm Bull" 3893-33 3898, 1985

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      22 "Greentea upregulates the low-density lipoprotein receptor throughthe sterol-regulated element binding Protein in HepG2 livercells. J Agric Food Chem. 49" 49 : 5639-5645, 2001

      23 "Goldstein JL. Nuclear protein that binds sterol regulatory ele-ment of low density lipoprotein receptor promoter. I. Identi-fication of the protein and delineation of its target nucleotide166 Lim" 14490-14496, 1993

      24 "Effect of ginseng saponins on cholesterol metabolism.I. Effect of ginsenoside-Rb on cholesterol synthesis in ratsfed on high-fat diet. Chem Pharm Bul" 2844-26 2854, 1978

      25 "Efect of ginseng saponins on cholesterol metabolism. I.The level and the synthesis of serum and liver cholesterol inrats treated with ginsenosides. Chem Pharm Bull" 1009-23 1016, 1975

      26 "Efect of ginseng saponins on cholesterol metab-olism. II. Effect of ginsenosides on cholesterol synthesis byliver slice. Chem Pharm Bull" 2985-24 2987, 1976

      27 "Dietaryginsenosides improve endothelium-dependent relaxation inthe thoracic aorta of hypercholesterolemic rabbit. Gen Phar-macol. 26" 26 : 483-487, 1995

      28 "Devaraj SN. Effect of tincture of Crataegus on the LDL-receptor activity of hepatic plasma membrane of rats fed anatherogenic diet. Atherosclerosis. 123" 123 : 235-241, 1996

      29 "Conjugated linoleic acid upregulates LDL receptor geneexpression in HepG2 cells. J Nutr. 134" 134 : 68-71, 2004

      30 "Comparison of synthetic saponincholesterol absorption inhibitors in rabbits evidence for anon-stoichiometric intestinal mechanism of action. J LipidRes. 40" 40 : 464-474, 1999

      31 "Cleav-age of sterol regulatory element-binding proteins at site-1 requires interaction with SREBP cleavage-activat-ing protein. Evidence from in vivo competition studies. JBiol Chem. 273" 273 : 5785-5793, 1998

      32 "Brown MS. Regulation of the mevalonatepathway. Nature. 343" 425-430, 1990

      33 "Autocatalytic processing of site-1 protease removes propep-tide and permits cleavage of sterol regulatory element-bind-ing proteins. J Biol Chem. 274" 274 : 22795-22804, 1999

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      2023 평가예정 해외DB학술지평가 신청대상 (해외등재 학술지 평가)
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      학술지 인용정보

      학술지 인용정보
      기준연도 WOS-KCI 통합IF(2년) KCIF(2년) KCIF(3년)
      2016 3.97 1.04 2.93
      KCIF(4년) KCIF(5년) 중심성지수(3년) 즉시성지수
      2.49 2.07 1.604 0.15
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