PMID- 22160327 OWN - NLM STAT- MEDLINE DCOM- 20120412 LR - 20211021 IS - 1875-8355 (Electronic) IS - 1572-3887 (Print) IS - 1572-3887 (Linking) VI - 31 IP - 1 DP - 2012 Jan TI - The adaptor-related protein complex 2, alpha 2 subunit (AP2alpha2) gene is a peroxisome proliferator-activated receptor cardiac target gene. PG - 75-83 LID - 10.1007/s10930-011-9379-0 [doi] AB - A peroxisome proliferator-actived receptor (PPAR) response element (RE) in the promoter region of the adaptor-related protein complex 2, alpha 2 subunit (AP2alpha2) 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 AP2alpha2 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 delta337T thyroid hormone receptor (TRbeta1) transgenic mice. Heart tissue was extracted and AP2alpha2 gene expression was compared using Affymetrix expression arrays and qRT PCR among four groups [control, control with Wy14643, delta337T TRbeta1 and delta337T TRbeta1 with Wy14643]. The gene expression of AP2alpha2 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 AP2alpha2 promoter were used in EMSA to verify binding of the PPAR and RXR receptors to their REs. pGL4.0 [Luc] constructs of the AP2alpha2 promoter with and without the PPAR/RXR motifs were co-transfected with mouse PPARalpha, beta or gamma1 into HepG2 cells and used in lucerifase assays to verify gene activation. In conclusion our study revealed that PPARalpha regulates the mouse cardiac AP2alpha2 gene in both the control and transgenic mouse. FAU - Buroker, Norman E AU - Buroker NE AD - Department of Cardiology, Seattle Children's Research Institute, Seattle, WA 98101, USA. nburoker@u.washington.edu FAU - Huang, Jie-Yu AU - Huang JY FAU - Barboza, Julia AU - Barboza J FAU - Ledee, Dolena R AU - Ledee DR FAU - Eastman, Rocky J Jr AU - Eastman RJ Jr FAU - Reinecke, Hans AU - Reinecke H FAU - Ning, Xue-Han AU - Ning XH FAU - Bassuk, James A AU - Bassuk JA FAU - Portman, Michael A AU - Portman MA LA - eng GR - R01 HL060666/HL/NHLBI NIH HHS/United States GR - R01-HL-60666/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - Netherlands TA - Protein J JT - The protein journal JID - 101212092 RN - 0 (Adaptor Protein Complex 2) RN - 0 (Adaptor Protein Complex alpha Subunits) RN - 0 (PPAR alpha) RN - 0 (adaptor protein complex 2, alpha 2 subunit) SB - IM MH - Adaptor Protein Complex 2/*genetics/metabolism MH - Adaptor Protein Complex alpha Subunits/*genetics/metabolism MH - Animals MH - Cell Line MH - Gene Expression Regulation MH - Humans MH - Mice MH - Mice, Transgenic MH - Myocardium/*metabolism MH - PPAR alpha/genetics/*metabolism MH - Promoter Regions, Genetic MH - Response Elements MH - *Up-Regulation PMC - PMC3699174 MID - NIHMS480932 EDAT- 2011/12/14 06:00 MHDA- 2012/04/13 06:00 PMCR- 2013/07/02 CRDT- 2011/12/14 06:00 PHST- 2011/12/14 06:00 [entrez] PHST- 2011/12/14 06:00 [pubmed] PHST- 2012/04/13 06:00 [medline] PHST- 2013/07/02 00:00 [pmc-release] AID - 10.1007/s10930-011-9379-0 [doi] PST - ppublish SO - Protein J. 2012 Jan;31(1):75-83. doi: 10.1007/s10930-011-9379-0.