ROS mediates p300-dependent STAT1 interaction with PPAR{gamma} in CD36 expression and foam cell formation [Lipids]

October 25th, 2015 by Kotla, S., Rao, G. N.

Previously we have demonstrated that 15(S)-HETE induces CD36 expression involving STAT1. Many studies have shown that PPARγ mediates CD36 expression. Therefore, we asked the question whether these transcriptional factors interact with each other in the regulation of CD36 expression by 15(S)-HETE. Here we show that STAT1 interacts with PPARγ in the induction of CD36 expression and foam cell formation by 15(S)-HETE. In addition, using molecular biological approaches such as EMSA, supershift EMSA, ChIP, re-ChIP and promoter-reporter gene assays, we demonstrate that the STAT1 and PPARγ complex binds to STAT binding site at -107 nt in the CD36 promoter and enhances its activity. Furthermore, the interaction of STAT1 with PPARγ depends on STAT1 acetylation, which is mediated by p300. In addition, our findings show that ROS-dependent Syk and Pyk2 stimulation is required for p300 tyrosine phosphorylation and activation. Together, these results demonstrate that an interaction between p300, STAT1 and PPARγ is required for 15(S)-HETE-induced CD36 expression, oxLDL uptake and foam cell formation, critical events underlying the pathogenesis of atherosclerosis.