PPARdelta increases expression of the human apolipoprotein A-II gene in human liver cells.
The peroxisome proliferator-activated receptor delta (PPARdelta) is a transcription factor that regulates genes of importance in lipid and glucose metabolism. ApoA-II is one of the major proteins of the HDL-particle. The aim of this study was to investigate the regulation of apoA-II gene expression by PPARdelta. Treatment of HepG2 cells with the PPARdelta specific agonist GW501516 increased apoA-II mRNA expression. Likewise, reporter gene assays using a construct containing 2.7 kb of the proximal apoA-II promoter showed increased activity after treatment with GW501516, both in HepG2 and in HuH-7 cells. Mutation of two putative PPAR response elements (PPREs) in this region showed that the PPRE at position -737/-717 is the functional site. Binding of PPARdelta to this site was confirmed by chromatin immunoprecipitation and gel retardation analyses. In conclusion, PPARdelta increases the expression of the human apoA-II gene in liver cells via a PPRE in the proximal promoter.
Thulin
Petra
P
Atherosclerosis Research Unit, Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, SE-171 76 Stockholm, Sweden. petra.thulin@ki.se
Glinghammar
Björn
B
Skogsberg
Josefin
J
Lundell
Kerstin
K
Ehrenborg
Ewa
E
D016633:Apolipoprotein A-II / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D050260:Carbohydrate Metabolism / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation / Q000379:methods; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects; D009154:Mutation; D047494:PPAR delta / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D020218:Response Elements / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D013844:Thiazoles / Q000494:pharmacology*
C115794:APOA2 protein, human; D016633:Apolipoprotein A-II; C425931:GW 501516; D047494:PPAR delta; D013844:Thiazoles