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

Kotla, Sivareddy; Rao, Gadiparthi N.

doi:10.1074/jbc.m115.686865

Cited by 26 publications

(25 citation statements)

References 62 publications

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“…Previously, we have reported that ROS are involved in the activation of Syk and Pyk2 in 15(S)-HETE-induced p300 tyrosine phosphorylation, STAT1 acetylation and its interaction with PPARγ in CD36 expression, oxLDL uptake and foam cell formation [27]. Therefore, we tested the role of ROS in CC-induced BTK activation, p300 tyrosine phosphorylation, STAT1 acetylation and its interaction with PPARγ in CD36 expression, oxLDL uptake and foam cell formation.…”

Section: Resultsmentioning

confidence: 94%

“…We have previously shown that STAT1, PPARγ and p300 bind to a STAT-binding site in CD36 promoter and enhance its activity in response to a lipid hydroperoxide, 15(S)-HETE [27]. In lieu of these observations, we asked the question whether these transcriptional factors and coactivator have any role in CC-induced CD36 promoter activity.…”

Section: Resultsmentioning

confidence: 97%

“…These results suggest that CC induce oxLDL uptake and foam cell formation via CD36 expression. Studies from others as well as our laboratories have shown a role for STAT1 in CD36 expression [27], [28]. To test the role of STATs in CC-induced CD36 expression, oxLDL uptake and foam cell formation, we have studied the effects of CC on STAT1, STAT2, STAT3, STAT4, STAT5 and STAT6 activation.…”

Section: Resultsmentioning

confidence: 99%

“…4A). Previously, we have shown that non-receptor tyrosine kinases (NRTKs) Syk and Pyk2 were involved in 15(S)-HETE-induced p300 tyrosine phosphorylation and its activation leading to STAT1 acetylation and its interaction with PPARγ in CD36 expression, oxLDL uptake and foam cell formation [27]. To identify NRTK that mediates CC-induced p300 tyrosine phosphorylation, we first studied the time course effect of CC on tyrosine phosphorylation and activation of various NRTKs.…”

Section: Resultsmentioning

confidence: 99%

“…Therefore, scavenger receptor expression is likely a determinant factor for oxLDL uptake by cells such as macrophages. In this context, among the many scavenger receptors, CD36 has been shown to be a major mediator of oxLDL uptake and foam cell formation [25], [27], [41]. Despite the advancement in our understating between cellular cholesterol levels and scavenger receptor expression, the underlying mechanisms of their induction were not clear.…”

Section: Discussionmentioning

confidence: 99%

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ROS via BTK-p300-STAT1-PPARγ signaling activation mediates cholesterol crystals-induced CD36 expression and foam cell formation

2017

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In understanding the mechanisms of cholesterol in the pathogenesis of atherosclerosis, previous studies from other laboratories have demonstrated that cholesterol crystals (CC) induce scavenger receptor CD36 expression and NLRP3-mediated inflammasome formation. In elucidating the mechanisms by which CC could enhance CD36 expression and foam cell formation, here we report that CC via NADPH and xanthine oxidases-mediated ROS production activates BTK, a non-receptor tyrosine kinase. In addition, CC induce p300 tyrosine phosphorylation and activation in a BTK-dependent manner, which in turn, leads to STAT1 acetylation and its interaction with PPARγ in CD36 expression, oxLDL uptake and foam cell formation. Furthermore, p300, STAT1 and PPARγ bound to a STAT binding site at −107 nt in CD36 promoter and enhanced its activity in ROS and BTK-dependent manner. Disruption of this STAT binding site by site-directed mutagenesis abolished CC-induced CD36 promoter activity. Together these results reveal for the first time that CC via producing ROS and activating BTK causes p300-mediated STAT1 acetylation and its interaction with PPARγ in CD36 expression, oxLDL uptake and foam cell formation.

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Section: Resultsmentioning

confidence: 94%

Section: Resultsmentioning

confidence: 97%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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ROS via BTK-p300-STAT1-PPARγ signaling activation mediates cholesterol crystals-induced CD36 expression and foam cell formation

2017

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ox‐LDL increases microRNA‐29a transcription through upregulating YY1 and STAT1 in macrophages

Jian

Dai

Yao

et al. 2017

Cell Biology International

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Macrophages and oxidized low-density lipoprotein (ox-LDL) have been verified playing vital roles in the pathogenesis of atherosclerosis (AS). Previous studies demonstrated that microRNA-29a (miR-29a) was upregulated in many atherogenic process and cells, thus acting as an important participant in AS. But the detailed regulation mechanism of miR-29a in AS has not been fully understood. In our study, we demonstrated a positive feedback loop of ox-LDL-SRA-miR-29a. Furthermore, we found that YY1 and STAT1 were upregulated in ox-LDL-stimulating macrophages followed by translocation in the nucleus and binding to the transcriptional promoter region of miR-29a, thus leading to the increase of miR-29a expression. In addition, we demonstrated that JAK1/2 signaling was involved in miR-29a upregulation. Finally, we found that miR-29a played important roles in the secretion of proinflammation factors and lipid uptake in macrophages. We uncovered the molecular mechanism and provide novel insights into the function and regulatory network of miR-29a expression regulated by ox-LDL in macrophages.

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The effect of maternal exposure to di‐(2‐ethylhexyl)‐phthalate on fetal cardiac development in mice

Tang

Deng²,

Duan

et al. 2018

J of Applied Toxicology

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Accumulating evidence has suggested a link between maternal di-(2-ethylhexyl)-phthalate (DEHP) exposure and various developmental abnormalities. However, the evidence regarding the effect of maternal DEHP exposure on fetal cardiac development is scarce. The present study aimed to determine the effect of maternal DEHP exposure on fetal cardiac development in mice and explore the possible involved mechanism preliminarily. The C57BL mice were randomly divided into four groups: the vehicle group (corn oil, n = 10), 250 mg kg DEHP group (n = 15), 500 mg kg DEHP group (n = 20) and 1 g kg DEHP group (n = 20). Pregnant dams in different group received respective intervention by gavage once daily from embryonic day (E)6.5 to E14.5. Maternal weights were monitored every day and samples were collected at E15.5. Hematoxylin and eosin staining was used to examine fetal cardiac malformations. Real-time quantitative polymerase chain reaction and western blot were applied to detect peroxisome proliferator-activated receptor (PPAR)α/PPARγ/Nkx2.5/Gata4/Tbx5/Mef2c/Chf1 mRNA and protein expression, respectively. Maternal DEHP exposure significantly decreased maternal body weight, fetal weight and placental weight, and remarkably elevated fetal cardiac malformations rate. The phenotypes of cardiac anomalies mainly include septal defects, ventricular myocardium noncompaction and cardiac hypoplasia. Higher doses DEHP (500 mg kg and 1 g kg ) could significantly decreased fetal cardiac Gata4/Mef2c/Chf1 expression, while PPARγ expression was upregulated. Maternal exposure to higher doses of DEHP could result in fetal cardiac development malformations in mice and it might have resulted from the inhibition of cardiac GATA4/Mef2c/Chf1 expression via PPARγ activation.

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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

Cited by 26 publications

References 62 publications

ROS via BTK-p300-STAT1-PPARγ signaling activation mediates cholesterol crystals-induced CD36 expression and foam cell formation

ROS via BTK-p300-STAT1-PPARγ signaling activation mediates cholesterol crystals-induced CD36 expression and foam cell formation

ox‐LDL increases microRNA‐29a transcription through upregulating YY1 and STAT1 in macrophages

The effect of maternal exposure to di‐(2‐ethylhexyl)‐phthalate on fetal cardiac development in mice

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