Abstract
Previously, we have demonstrated that 15(S)-hydroxyeicosatetranoic acid (15(S)-HETE) induces CD36 expression involving STAT1. Many studies have shown that peroxisome proliferator-activated receptor (PPAR)-γ 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 the STAT-binding site at -107 nucleotides 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 reactive oxygen species-dependent Syk and Pyk2 stimulation is required for p300 tyrosine phosphorylation and activation. Together, these results demonstrate that an interaction between STAT1, p300, and peroxisome proliferator-activated receptor-γ is required for 15(S)-HETE-induced CD36 expression, oxidized low density lipoprotein uptake, and foam cell formation, critical events underlying the pathogenesis of atherosclerosis.
Highlights
CD36 plays a role in lipid uptake, foam cell formation, and atherogenesis
We have demonstrated that 15(S)-HETE induces CD36 expression and foam cell formation involving STAT1 [24]
Coimmunoprecipitation experiment revealed that STAT1 exists in complex with peroxisome proliferatoractivated receptor (PPAR)␣, PPAR, and PPAR␦ constitutively, and in response to 15(S)-HETE, its association with PPAR␥ increases in a time-dependent manner with maximum effect at FIGURE 1. 15(S)-HETE stimulates STAT1 association with PPAR␥ in the induction of CD36 expression
Summary
Results: 15(S)-HETE induces CD36 expression and foam cell formation by triggering p300-mediated STAT1 acetylation and its interaction with PPAR␥. We have demonstrated that 15(S)-hydroxyeicosatetranoic acid (15(S)-HETE) induces CD36 expression involving STAT1. Many studies have shown that peroxisome proliferatoractivated receptor (PPAR)-␥ mediates CD36 expression. The interaction of STAT1 with PPAR␥ depends on STAT1 acetylation, which is mediated by p300. Our findings show that reactive oxygen species-dependent Syk and Pyk stimulation is required for p300 tyrosine phosphorylation and activation. Together, these results demonstrate that an interaction between STAT1, p300, and peroxisome proliferator-activated receptor-␥ is required for 15(S)-HETE-induced CD36 expression, oxidized low density lipoprotein uptake, and foam cell formation, critical events underlying the pathogenesis of atherosclerosis
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
