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Article: Ethanol down-regulates the transcription of microsomal triglyceride transfer protein gene

TitleEthanol down-regulates the transcription of microsomal triglyceride transfer protein gene
Authors
Issue Date1997
PublisherFederation of American Societies for Experimental Biology. The Journal's web site is located at http://www.fasebj.org/
Citation
FASEB Journal, 1997, v. 11 n. 13, p. 1145-1152 How to Cite?
AbstractMicrosomal triglyceride transfer protein (MTP) plays a central role in the assembly and secretion of apoB-containing lipoproteins. In this study, we investigated the effect of ethanol on the expression of the large subunit of MTP in a human liver hepatoma cell line, the HepG2 cells. Exposure of HepG2 cells to low concentrations of ethanol reduced MTP mRNA levels in a concentration- and time-dependent manner. The level of MTP mRNA decreased significantly (P<0.05, -20% relative to pretreatment control) when the concentration of ethanol in the culture medium was 50 ppm (0.005%, v/v). Maximal suppression (-50%) was observed at 100 ppm ethanol; the MTP mRNA levels remained at 50% of control when the ethanol concentration was raised to 10,000 ppm. Furthermore, a 10-day ethanol treatment caused a significant 50% decrease in the MTP activity and apoB secretion rate in HepG2 cells. To investigate the molecular mechanisms underlying this phenomenon, we examined the effect of ethanol on the promoter activity of the MTP gene. Transient transfection analysis of human MTP promoter-driven luciferase gene expression showed that ethanol down-regulates MTP promoter activity in a manner parallel to that observed for mRNA levels. Deletion analysis suggested that the MTP promoter sequence contains a negative ethanol response element 612 to -142 bp upstream of the transcription start site. To evaluate the in vivo relevance of the effect of ethanol on MTP mRNA levels, rats were given a single oral dose of ethanol, with hepatic and intestinal MTP mRNA measured 3 h after dosing. Rats receiving 1 or 3 g/kg of ethanol exhibited substantially lower hepatic and intestinal MTP mRNA levels. Taken together, these results strongly suggest that ethanol can modulate the secretion of apoB-containing lipoproteins by down-regulating the expression of MTP large subunit, primarily through inhibiting the transcription of the MTP gene.
Persistent Identifierhttp://hdl.handle.net/10722/167560
ISSN
2015 Impact Factor: 5.299
2015 SCImago Journal Rankings: 2.775
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLin, MCMen_US
dc.contributor.authorLi, JJen_US
dc.contributor.authorWang, EJen_US
dc.contributor.authorPrincler, GLen_US
dc.contributor.authorKauffman, FCen_US
dc.contributor.authorKung, HFen_US
dc.date.accessioned2012-10-08T03:08:31Z-
dc.date.available2012-10-08T03:08:31Z-
dc.date.issued1997en_US
dc.identifier.citationFASEB Journal, 1997, v. 11 n. 13, p. 1145-1152en_US
dc.identifier.issn0892-6638en_US
dc.identifier.urihttp://hdl.handle.net/10722/167560-
dc.description.abstractMicrosomal triglyceride transfer protein (MTP) plays a central role in the assembly and secretion of apoB-containing lipoproteins. In this study, we investigated the effect of ethanol on the expression of the large subunit of MTP in a human liver hepatoma cell line, the HepG2 cells. Exposure of HepG2 cells to low concentrations of ethanol reduced MTP mRNA levels in a concentration- and time-dependent manner. The level of MTP mRNA decreased significantly (P<0.05, -20% relative to pretreatment control) when the concentration of ethanol in the culture medium was 50 ppm (0.005%, v/v). Maximal suppression (-50%) was observed at 100 ppm ethanol; the MTP mRNA levels remained at 50% of control when the ethanol concentration was raised to 10,000 ppm. Furthermore, a 10-day ethanol treatment caused a significant 50% decrease in the MTP activity and apoB secretion rate in HepG2 cells. To investigate the molecular mechanisms underlying this phenomenon, we examined the effect of ethanol on the promoter activity of the MTP gene. Transient transfection analysis of human MTP promoter-driven luciferase gene expression showed that ethanol down-regulates MTP promoter activity in a manner parallel to that observed for mRNA levels. Deletion analysis suggested that the MTP promoter sequence contains a negative ethanol response element 612 to -142 bp upstream of the transcription start site. To evaluate the in vivo relevance of the effect of ethanol on MTP mRNA levels, rats were given a single oral dose of ethanol, with hepatic and intestinal MTP mRNA measured 3 h after dosing. Rats receiving 1 or 3 g/kg of ethanol exhibited substantially lower hepatic and intestinal MTP mRNA levels. Taken together, these results strongly suggest that ethanol can modulate the secretion of apoB-containing lipoproteins by down-regulating the expression of MTP large subunit, primarily through inhibiting the transcription of the MTP gene.en_US
dc.languageengen_US
dc.publisherFederation of American Societies for Experimental Biology. The Journal's web site is located at http://www.fasebj.org/en_US
dc.relation.ispartofFASEB Journalen_US
dc.subject.meshAnimalsen_US
dc.subject.meshApolipoproteins B - Biosynthesisen_US
dc.subject.meshCarcinoma, Hepatocellularen_US
dc.subject.meshCarrier Proteins - Biosynthesis - Geneticsen_US
dc.subject.meshEthanol - Pharmacologyen_US
dc.subject.meshGene Expression Regulation - Drug Effectsen_US
dc.subject.meshHumansen_US
dc.subject.meshIntestines - Metabolismen_US
dc.subject.meshKineticsen_US
dc.subject.meshLiver - Metabolismen_US
dc.subject.meshLiver Neoplasmsen_US
dc.subject.meshLuciferases - Biosynthesisen_US
dc.subject.meshMacromolecular Substancesen_US
dc.subject.meshMaleen_US
dc.subject.meshMicrosomes - Metabolismen_US
dc.subject.meshPromoter Regions, Geneticen_US
dc.subject.meshRna, Messenger - Biosynthesisen_US
dc.subject.meshRatsen_US
dc.subject.meshRats, Sprague-Dawleyen_US
dc.subject.meshRecombinant Fusion Proteins - Biosynthesisen_US
dc.subject.meshSequence Deletionen_US
dc.subject.meshTime Factorsen_US
dc.subject.meshTranscription, Genetic - Drug Effectsen_US
dc.subject.meshTransfectionen_US
dc.subject.meshTumor Cells, Cultureden_US
dc.titleEthanol down-regulates the transcription of microsomal triglyceride transfer protein geneen_US
dc.typeArticleen_US
dc.identifier.emailLin, MCM:mcllin@hkucc.hku.hken_US
dc.identifier.authorityLin, MCM=rp00746en_US
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.pmid9367349-
dc.identifier.scopuseid_2-s2.0-0030727657en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0030727657&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume11en_US
dc.identifier.issue13en_US
dc.identifier.spage1145en_US
dc.identifier.epage1152en_US
dc.identifier.isiWOS:A1997YE98300012-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridLin, MCM=7404816359en_US
dc.identifier.scopusauthoridLi, JJ=26643419700en_US
dc.identifier.scopusauthoridWang, EJ=7403414471en_US
dc.identifier.scopusauthoridPrincler, GL=6701541544en_US
dc.identifier.scopusauthoridKauffman, FC=7005992097en_US
dc.identifier.scopusauthoridKung, HF=7402514190en_US

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