analysis of the heat shock response in mouse liver reveals transcriptional dependence on the nuclear receptor peroxisome proliferator-activated receptor α (pparα)小鼠肝脏的热休克反应的分析,将揭示转录依赖核受体的过氧物酶体proliferator-activated受体α(pparα).pdfVIP

Vallanat et al. BMC Genomics 2010, 11:16 /1471-2164/11/16 RESEARCH ARTICLE Open Access Analysis of the heat shock response in mouse liver reveals transcriptional dependence on the nuclear receptor peroxisome proliferator- activated receptor a (PPARa) 1 2 3 1 4 Beena Vallanat , Steven P Anderson , Holly M Brown-Borg , Hongzu Ren , Sander Kersten , 5 5,6 1* Sudhakar Jonnalagadda , Rajagopalan Srinivasan , J Christopher Corton Abstract Background: The nuclear receptor peroxisome proliferator-activated receptor alpha (PPARa) regulates responses to chemical or physical stress in part by altering expression of genes involved in proteome maintenance. Many of these genes are also transcriptionally regulated by heat shock (HS) through activation by HS factor-1 (HSF1). We hypothesized that there are interactions on a genetic level between PPARa and the HS response mediated by HSF1. Results: Wild-type and PPARa-null mice were exposed to HS, the PPARa agonist WY-14,643 (WY), or both; gene and protein expression was examined in the livers of the mice 4 or 24 hrs after HS. Gene expression profiling identified a number of Hsp family members that were altered similarly in both mouse strains. However, most of the targets of HS did not overlap between strains. A subset of genes was shown by microarray and RT-PCR to be regulated by HS in a PPARa-dependent manner. HS also down-regulated a large set of mitochondrial genes specifically in PPARa-null mice that are known targets of PPARg co-activator-1 (PGC-1) family members. Pretreatment of PPARa-null mice with WY increased expression of PGC-1b and target genes and prevented the down-regulati