Reactive Oxygen Species (ROS) Mediate p300-dependent STAT1 Protein Interaction with Peroxisome Proliferator-activated Receptor (PPAR)-γ in CD36 Protein Expression and Foam Cell Formation
Authors: Gadiparthi N Rao
Sivareddy Kotla
Journal: Journal of Biological Chemistry (2015)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: 15(S)-HETE; cd36; foam cell; gene expression; lipid
Affiliations: From the Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee 38163., From the Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee 38163 .

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. 

Retracted: Yes

PubPeer comments:
 Figures 2D and 3D (updated with additional findings by Twitter users) * Red boxes: The GW9662 Vehicle panel in Figure 2D appears to overlap with the pcDNA panel in Figure 3D * Green boxes: The PFS1YF 15(S) HETE panel in Figure 2D appears to overlap with the p300WT_15S-HETE panel in Figure 3D, if one of the panels is mirrored and rotated * Blue boxes: The p300WT and pcDNA_15(S)-HETE panels in Figure 3D appear to overlap with a different aspect ratio Can the authors clarify if these are showing the same sample, please? ![file] , 
 Necessary action is being taken. , 
 Thank you, Dr. Rao. Could you be a bit more specific than  Necessary action is being taken , please? How would you explain the stretching and mirroring of images? Will you ask the journal to retract the paper? , 
 Withdrawal, 25 June 2022: https: www.jbc.org article S0021-9258(22)00594-4 fulltext#relatedArticles  This article has been withdrawn by the authors. The authors and the journal conclude that the images between and within Figures 2D and 3D were reused. Specifically, the image u201cpcDNAu201d in Figure 3D was a duplication of the image u201cGW9662 + Vehicleu201d in Figure 2D. Similarly, the image u201cp300WT + 15(S)-HETEu201d in Figure 3D was captured from the well u201cPFS1YF + 15(S)-HETEu201d in Figure 2D. The image u201cp300WTu201d in Figure 3D was captured from the well u201cpcDNA + 15(S)-HETEu201d in Figure 3D itself. Additional potential internal reuse is in Figure 2D, STAT1(WT) + 15(S)-HETEu201d and Figure 2D, u201cPFS1YF + 15(S)-HETEu201d. The authors state that these image duplications do not affect the conclusions of the paper. The authors apologize for this oversight. Could the authors perhaps provide some clarify into how these duplications could have happened, perhaps? ,