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The hypolipidemic effect of cilostazol can be mediated by regulation of hepatic low-density lipoprotein receptor-related protein 1 (LRP 1) expression

DC FieldValueLanguage
dc.contributor.author강은석-
dc.contributor.author이병완-
dc.contributor.author이현철-
dc.contributor.author차봉수-
dc.date.accessioned2015-01-06T16:24:35Z-
dc.date.available2015-01-06T16:24:35Z-
dc.date.issued2014-
dc.identifier.issn0026-0495-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/98051-
dc.description.abstractOBJECTIVES: Cilostazol, a selective phosphodiesterase 3 (PDE3) inhibitor, is a vasodilator and an anti-thrombotic agent. The mechanism whereby cilostazol reduces plasma triglyceride is not completely understood. Here we investigated the effect of cilostazol on a remnant lipoprotein receptor, low-density lipoprotein receptor-related protein 1 (LRP1), which has been reported to play an essential role in clearance of circulating triglyceride in the liver. MATERIALS/METHODS: Total cellular expression, and functional and transcriptional regulation of LRP1 were analyzed in human hepatocarcinoma cell lines incubated with cilostazol. Also, C57BL/6 mice were subjected to high-fat diet (60% kcal) and cilostazol (30 mg/kg) treatment for 10 weeks. RESULTS: Cilostazol increased both mRNA and protein expression of LRP1 in HepG2 and Hep3B cells. In addition, enhanced transcriptional activity of the LRP1 promoter containing a peroxisome proliferator response element (PPRE) was observed after cilostazol exposure. Cilostazol treatment enhanced the uptake of lipidated apoE3, and this effect was abolished when LRP1 was silenced by siRNA knockdown. High-fat diet induced hyperglycemia with high level of plasma triglycerides, and reduced hepatic LRP1 expression in mice. Treatment with cilostazol for the same period of time, however, successfully prevented this down-regulation of LRP1 expression and reduced plasma triglycerides. CONCLUSION: Taken together, our results demonstrated that cilostazol enhances LRP1 expression in liver by activating PPARγ through the PPRE in the LRP1 promoter. Increased hepatic LRP1 may be essential for the reduction of circulating triglycerides brought about by cilostazol.-
dc.description.statementOfResponsibilityopen-
dc.format.extent112~119-
dc.relation.isPartOfMETABOLISM-CLINICAL AND EXPERIMENTAL-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAnimals-
dc.subject.MESHApolipoprotein E3/metabolism-
dc.subject.MESHBlotting, Western-
dc.subject.MESHCarcinoma, Hepatocellular/metabolism-
dc.subject.MESHCell Line, Tumor-
dc.subject.MESHDiet, High-Fat-
dc.subject.MESHDown-Regulation-
dc.subject.MESHGene Expression Regulation, Neoplastic-
dc.subject.MESHGene Silencing-
dc.subject.MESHHep G2 Cells-
dc.subject.MESHHumans-
dc.subject.MESHHypolipidemic Agents/pharmacology*-
dc.subject.MESHLiver/metabolism*-
dc.subject.MESHLiver Neoplasms/metabolism-
dc.subject.MESHLow Density Lipoprotein Receptor-Related Protein-1/drug effects-
dc.subject.MESHLow Density Lipoprotein Receptor-Related Protein-1/genetics-
dc.subject.MESHLow Density Lipoprotein Receptor-Related Protein-1/metabolism*-
dc.subject.MESHMice-
dc.subject.MESHMice, Inbred C57BL-
dc.subject.MESHReal-Time Polymerase Chain Reaction-
dc.subject.MESHTetrazoles/pharmacology*-
dc.subject.MESHTranscription, Genetic-
dc.subject.MESHTriglycerides/blood*-
dc.titleThe hypolipidemic effect of cilostazol can be mediated by regulation of hepatic low-density lipoprotein receptor-related protein 1 (LRP 1) expression-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Internal Medicine (내과학)-
dc.contributor.googleauthorHyung Jun Kim-
dc.contributor.googleauthorJae Hoon Moon-
dc.contributor.googleauthorHyun Min Kim-
dc.contributor.googleauthorMi Ra Yun-
dc.contributor.googleauthorByung Hun Jeon-
dc.contributor.googleauthorByungWan Lee-
dc.contributor.googleauthorEun Seok Kang-
dc.contributor.googleauthorHyun Chul Lee-
dc.contributor.googleauthorBong Soo Cha-
dc.identifier.doi10.1016/j.metabol.2013.09.006-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA00068-
dc.contributor.localIdA02796-
dc.contributor.localIdA03301-
dc.contributor.localIdA03996-
dc.relation.journalcodeJ02223-
dc.identifier.eissn1532-8600-
dc.identifier.pmid24139096-
dc.identifier.urlhttp://www.sciencedirect.com/science/article/pii/S0026049513002904-
dc.subject.keyword1,2-dimyristoyl-sn-glycero-3-phosphocholin-
dc.subject.keyword2-chloro-5-nitrobenzanilide-
dc.subject.keyword3,3′-Diaminobenzidine-
dc.subject.keyword4′,6-diamidino-2-phenylindole-
dc.subject.keywordAtherosclerosis-
dc.subject.keywordCR-
dc.subject.keywordDAB-
dc.subject.keywordDAPI-
dc.subject.keywordDMPC-
dc.subject.keywordDMSO-
dc.subject.keywordDNase-
dc.subject.keywordDyslipidemia-
dc.subject.keywordGW9662-
dc.subject.keywordGlut 4-
dc.subject.keywordH&E-
dc.subject.keywordHDL-
dc.subject.keywordHSPG-
dc.subject.keywordHUVEC-
dc.subject.keywordIPGTT-
dc.subject.keywordLDL-
dc.subject.keywordLPL-
dc.subject.keywordLRP1-
dc.subject.keywordMEM-
dc.subject.keywordPCR-
dc.subject.keywordPDE3-
dc.subject.keywordPPAR-γ-
dc.subject.keywordPPARγ-
dc.subject.keywordPPRE-
dc.subject.keywordPolymerase chain reaction-
dc.subject.keywordRNase-
dc.subject.keywordRT-
dc.subject.keywordRT-PCR-
dc.subject.keywordReverse transcriptase-
dc.subject.keywordSTZ-
dc.subject.keywordTG-
dc.subject.keywordVLDL-
dc.subject.keywordapoE-
dc.subject.keywordapolipoprotein E-
dc.subject.keywordchylomicron remnants-
dc.subject.keyworddNTP-
dc.subject.keyworddeoxyriboNTP-
dc.subject.keyworddeoxyribonuclease-
dc.subject.keyworddimethyl sulfoxide-
dc.subject.keywordglucose transporter 4-
dc.subject.keywordhematoxylin and eosin-
dc.subject.keywordheparan sulfate proteoglycans-
dc.subject.keywordhigh-density lipoprotein-
dc.subject.keywordhuman umbilical vein endothelia cell-
dc.subject.keywordi.p. glucose tolerance test-
dc.subject.keywordlipoprotein lipase-
dc.subject.keywordlow-density lipoprotein-
dc.subject.keywordlow-density lipoprotein receptor-related protein 1-
dc.subject.keywordminimum essential medium-
dc.subject.keywordperoxisome proliferator activated receptor-γ-
dc.subject.keywordperoxisome proliferator response element-
dc.subject.keywordphosphodiesterase 3-
dc.subject.keywordreal-time polymerase chain reaction-
dc.subject.keywordribonuclease-
dc.subject.keywordsiRNA-
dc.subject.keywordsmall interfering RNA-
dc.subject.keywordPKA, protein kinase A-
dc.subject.keywordstreptozotocin-
dc.subject.keywordtriglyceride-
dc.subject.keywordvery low-density lipoproteins-
dc.contributor.alternativeNameKang, Eun Seok-
dc.contributor.alternativeNameLee, Byung Wan-
dc.contributor.alternativeNameLee, Hyun Chul-
dc.contributor.alternativeNameCha, Bong Soo-
dc.contributor.affiliatedAuthorKang, Eun Seok-
dc.contributor.affiliatedAuthorLee, Byung Wan-
dc.contributor.affiliatedAuthorLee, Hyun Chul-
dc.contributor.affiliatedAuthorCha, Bong Soo-
dc.rights.accessRightsfree-
dc.citation.volume63-
dc.citation.number1-
dc.citation.startPage112-
dc.citation.endPage119-
dc.identifier.bibliographicCitationMETABOLISM-CLINICAL AND EXPERIMENTAL, Vol.63(1) : 112-119, 2014-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers

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