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Dimethyl sulfoxide reduces hepatocellular lipid accumulation through autophagy induction

DC FieldValueLanguage
dc.contributor.author송영미-
dc.contributor.author이병완-
dc.contributor.author이현철-
dc.contributor.author차봉수-
dc.contributor.author강은석-
dc.contributor.author송선옥-
dc.date.accessioned2014-12-19T16:31:25Z-
dc.date.available2014-12-19T16:31:25Z-
dc.date.issued2012-
dc.identifier.issn1554-8627-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/89690-
dc.description.abstractInduction of autophagy is known not only to regulate cellular homeostasis but also to decrease triglyceride accumulation in hepatocytes. The aim of this study is to investigate whether DMSO (dimethyl sulfoxide) has a beneficial role in free fatty acid-induced hepatic fat accumulation. In HepG2 cells, treatment with 0.5 mM palmitate for six hours significantly increased lipid and triglyceride (TG) accumulation, assessed by Oil-red O staining and TG quantification assay. Treatment with 0.01% DMSO for 16 h statistically reduced palmitate-induced TG contents. Pretreatment of 10 mM 3-methyladenine (3MA) for 2 h restored hepatocellular lipid contents, which were attenuated by treatment with DMSO. DMSO increased LC3-II conversion and decreased SQSTM1/p62 expression in a time and dose-dependent manner. In addition, the number of autophagosomes and autolysosomes, as seen under an electron microscopy, as well as the percentage of RFP-LAMP1 colocalized with GFP-LC3 dots in cells transfected with both GFP-LC3 and RFP-LAMP1, as seen under a fluorescent microscopy, also increased in DMSO-treated HepG2 cells. DMSO also suppressed p-eIF2α/p-EIF2S1, ATF4, p-AKT1, p-MTOR and p-p70s6k/p-RPS6KB2 expression as assessed by western blotting. Knockdown of ATF4 expression using siRNA suppressed ATF4 expression and phosphorylation of AKT1, MTOR and RPS6KB2, but increased LC3-II conversion. DMSO reduced not only soluble but also insoluble mtHTT (mutant huntingtin aggregates) expressions, which were masked in the presence of autophagy inhibitor. DMSO, a kind of chemical chaperone, activated autophagy by suppressing ATF4 expression and might play a protective role in the development of fatty acid-induced hepatosteatosis.-
dc.description.statementOfResponsibilityopen-
dc.relation.isPartOfAUTOPHAGY-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHActivating Transcription Factor 4/metabolism-
dc.subject.MESHAutophagy/drug effects*-
dc.subject.MESHBiomarkers/metabolism-
dc.subject.MESHCell Proliferation/drug effects-
dc.subject.MESHDimethyl Sulfoxide/pharmacology*-
dc.subject.MESHDown-Regulation/drug effects-
dc.subject.MESHEndoplasmic Reticulum Stress/drug effects-
dc.subject.MESHHep G2 Cells-
dc.subject.MESHHepatocytes/cytology*-
dc.subject.MESHHepatocytes/drug effects-
dc.subject.MESHHepatocytes/metabolism*-
dc.subject.MESHHepatocytes/ultrastructure-
dc.subject.MESHHumans-
dc.subject.MESHLipid Metabolism/drug effects*-
dc.subject.MESHPalmitic Acid/pharmacology-
dc.subject.MESHPeptides/chemistry-
dc.subject.MESHPeptides/metabolism-
dc.subject.MESHPhosphorylation/drug effects-
dc.subject.MESHProtein Structure, Quaternary-
dc.subject.MESHProto-Oncogene Proteins c-akt/metabolism-
dc.titleDimethyl sulfoxide reduces hepatocellular lipid accumulation through autophagy induction-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentYonsei Biomedical Research Center (연세의생명연구원)-
dc.contributor.googleauthorYoung Mi Song-
dc.contributor.googleauthorSun-Ok Song-
dc.contributor.googleauthorYong-Keun Jung-
dc.contributor.googleauthorEun-Seok Kang-
dc.contributor.googleauthorBong Soo Cha-
dc.contributor.googleauthorHyun Chul Lee-
dc.contributor.googleauthorByung-Wan Lee-
dc.identifier.doi22722716-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA02039-
dc.contributor.localIdA02796-
dc.contributor.localIdA03301-
dc.contributor.localIdA03996-
dc.contributor.localIdA00068-
dc.contributor.localIdA02029-
dc.relation.journalcodeJ00269-
dc.identifier.eissn1554-8635-
dc.identifier.pmid22722716-
dc.subject.keywordATF4-
dc.subject.keywordautophagy-
dc.subject.keyworddimethyl sulfoxide-
dc.subject.keywordhepatosteatosis-
dc.contributor.alternativeNameSong, Young Mi-
dc.contributor.alternativeNameLee, Byung Wan-
dc.contributor.alternativeNameLee, Hyun Chul-
dc.contributor.alternativeNameCha, Bong Soo-
dc.contributor.alternativeNameKang, Eun Seok-
dc.contributor.alternativeNameSong, Sun Ok-
dc.contributor.affiliatedAuthorSong, Young Mi-
dc.contributor.affiliatedAuthorLee, Byung Wan-
dc.contributor.affiliatedAuthorLee, Hyun Chul-
dc.contributor.affiliatedAuthorCha, Bong Soo-
dc.contributor.affiliatedAuthorKang, Eun Seok-
dc.contributor.affiliatedAuthorSong, Sun Ok-
dc.citation.volume8-
dc.citation.number7-
dc.citation.startPage1085-
dc.citation.endPage1097-
dc.identifier.bibliographicCitationAUTOPHAGY, Vol.8(7) : 1085-1097, 2012-
Appears in Collections:
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers

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