title: The adaptor-related protein complex 2, alpha 2 subunit (AP2α2) gene is a peroxisome proliferator-activated receptor cardiac target gene.
abstract: A peroxisome proliferator-actived receptor (PPAR) response element (RE) in the promoter region of the adaptor-related protein complex 2, alpha 2 subunit (AP2α2) of mouse heart has been identified. The steroid hormone nuclear PPARs and the retinoid X receptors (RXRs) are important transcriptional factors that regulate gene expression, cell differentiation and lipid metabolism. They form homo- (RXR) and hetero- (PPAR-RXR) dimers that bind DNA at various REs. The AP2α2 gene is part of complex and process that transports lipids and proteins from the plasma membrane to the endosomal system. A PPAR activator (Wy14643) and DMSO (vehicle) was introduced into control and δ337T thyroid hormone receptor (TRβ1) transgenic mice. Heart tissue was extracted and AP2α2 gene expression was compared using Affymetrix expression arrays and qRT PCR among four groups [control, control with Wy14643, δ337T TRβ1 and δ337T TRβ1 with Wy14643]. The gene expression of AP2α2 in the Wy14643 control and transgenic mouse groups was significantly up regulated over the vehicle mouse groups in both the array (p < 0.01) and qRT PCR (p < 0.01) studies. Duplex oligo DNAs containing the PPAR/RXR motif (AGGTCA/TCCAGT) from the AP2α2 promoter were used in EMSA to verify binding of the PPAR and RXR receptors to their REs. pGL4.0 [Luc] constructs of the AP2α2 promoter with and without the PPAR/RXR motifs were co-transfected with mouse PPARα, β or γ1 into HepG2 cells and used in lucerifase assays to verify gene activation. In conclusion our study revealed that PPARα regulates the mouse cardiac AP2α2 gene in both the control and transgenic mouse.
authors.affiliation: Department of Cardiology, Seattle Children's Research Institute, Seattle, WA 98101, USA. nburoker@u.washington.edu
authors.forename: Norman E
authors.initials: NE
authors.lastname: Buroker
authors.forename: Jie-Yu
authors.initials: JY
authors.lastname: Huang
authors.forename: Julia
authors.initials: J
authors.lastname: Barboza
authors.forename: Dolena R
authors.initials: DR
authors.lastname: Ledee
authors.forename: Rocky J
authors.initials: RJ
authors.lastname: Eastman
authors.forename: Hans
authors.initials: H
authors.lastname: Reinecke
authors.forename: Xue-Han
authors.initials: XH
authors.lastname: Ning
authors.forename: James A
authors.initials: JA
authors.lastname: Bassuk
authors.forename: Michael A
authors.initials: MA
authors.lastname: Portman
mesh_terms: D033962:Adaptor Protein Complex 2 / Q000235:genetics* / Q000378:metabolism; D033965:Adaptor Protein Complex alpha Subunits / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009206:Myocardium / Q000378:metabolism*; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D020218:Response Elements; D015854:Up-Regulation
chemical_list: D033962:Adaptor Protein Complex 2; D033965:Adaptor Protein Complex alpha Subunits; D047493:PPAR alpha; C439124:adaptor protein complex 2, alpha 2 subunit