title: Hepatitis C virus NS5A protein increases hepatic lipid accumulation via induction of activation and expression of PPARgamma.
abstract: Steatosis is an established risk factor for disease progression in cases of chronic hepatitis C. Recently it was demonstrated that Hepatitis C virus (HCV) core and non-structural (NS) 2 proteins (NS2) induce lipid accumulation in hepatic cells. However, it has yet to be determined whether other HCV proteins are associated with lipid metabolism. The NS5A augmented the transcriptional activity and gene expression of PPARgamma. Furthermore, NS5A increased the ability to recruit the transcriptional coactivator PGC-1s to the PPRE with PPARgamma, as well as the interaction with PPARgamma2 and PGC-1alpha. Our results indicate that NS5A may exploit multiple strategies that enhance PPARgamma-induced lipid accumulation.
authors.affiliation: Department of Molecular Biology, College of Natural Sciences, Pusan National University, Busan 609-735, Republic of Korea.
authors.forename: Kyeongjin
authors.initials: K
authors.lastname: Kim
authors.forename: Kook Hwan
authors.initials: KH
authors.lastname: Kim
authors.forename: Eunsin
authors.initials: E
authors.lastname: Ha
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Park
authors.forename: Naoya
authors.initials: N
authors.lastname: Sakamoto
authors.forename: Jaehun
authors.initials: J
authors.lastname: Cheong
mesh_terms: D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000378:metabolism; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D034622:RNA Interference; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism*; D012324:RNA-Dependent RNA Polymerase
chemical_list: D006360:Heat-Shock Proteins; D007004:Hypoglycemic Agents; D047495:PPAR gamma; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D000077154:Rosiglitazone; D045162:Thiazolidinediones; D014157:Transcription Factors; D017361:Viral Nonstructural Proteins; C486497:PPARGC1A protein, human; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase; C039671:ciglitazone