The adaptor-related protein complex 2, alpha 2 subunit (AP2?2) 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 (AP2?2) 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 AP2?2 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 ?337T thyroid hormone receptor (TR?1) transgenic mice. Heart tissue was extracted and AP2?2 gene expression was compared using Affymetrix expression arrays and qRT PCR among four groups [control, control with Wy14643, ?337T TR?1 and ?337T TR?1 with Wy14643]. The gene expression of AP2?2 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 AP2?2 promoter were used in EMSA to verify binding of the PPAR and RXR receptors to their REs. pGL4.0 [Luc] constructs of the AP2?2 promoter with and without the PPAR/RXR motifs were co-transfected with mouse PPAR?, ? or ?1 into HepG2 cells and used in lucerifase assays to verify gene activation. In conclusion our study revealed that PPAR? regulates the mouse cardiac AP2?2 gene in both the control and transgenic mouse.

SUBMITTER: Buroker NE 

PROVIDER: S-EPMC3699174 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature