scholarly journals 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

2015 ◽  
Vol 290 (51) ◽  
pp. 30306-30320 ◽  
Author(s):  
Sivareddy Kotla ◽  
Gadiparthi N. Rao
Keyword(s):  
Reactive Oxygen Species ◽  
Protein Interaction ◽  
Foam Cell ◽  
Cell Formation ◽  
Foam Cell Formation ◽  
Peroxisome Proliferator ◽  
Oxygen Species ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Stat1 Protein

scholarly journals Streptococcus sanguinis induces foam cell formation and cell death of macrophages in association with production of reactive oxygen species

2011 ◽  
Vol 323 (2) ◽  
pp. 164-170 ◽  
Author(s):  
Nobuo Okahashi ◽  
Toshinori Okinaga ◽  
Atsuo Sakurai ◽  
Yutaka Terao ◽  
Masanobu Nakata ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Foam Cell ◽  
Cell Formation ◽  
Reactive Oxygen ◽  
Foam Cell Formation ◽  
Oxygen Species ◽  
Streptococcus Sanguinis

scholarly journals Regulation of Macrophage Cholesterol Efflux through Hydroxymethylglutaryl-CoA Reductase Inhibition

2005 ◽  
Vol 280 (23) ◽  
pp. 22212-22221 ◽  
Author(s):  
Carmen A. Argmann ◽  
Jane Y. Edwards ◽  
Cynthia G. Sawyez ◽  
Caroline H. O'Neil ◽  
Robert A. Hegele ◽  
...  
Keyword(s):  
Cholesterol Efflux ◽  
Foam Cell ◽  
Cell Formation ◽  
Dominant Negative ◽  
Foam Cell Formation ◽  
Peroxisome Proliferator ◽  
Very Low Density Lipoproteins ◽  
Peroxisome Proliferator Activated Receptor ◽  
Abca1 Expression ◽  
Coa Reductase

The cholesterol biosynthetic pathway produces numerous signaling molecules. Oxysterols through liver X receptor (LXR) activation regulate cholesterol efflux, whereas the non-sterol mevalonate metabolite, geranylgeranyl pyrophosphate (GGPP), was recently demonstrated to inhibit ABCA1 expression directly, through antagonism of LXR and indirectly through enhanced RhoA geranylgeranylation. We used HMG-CoA reductase inhibitors (statins) to test the hypothesis that reduced synthesis of mevalonate metabolites would enhance cholesterol efflux and attenuate foam cell formation. Preincubation of THP-1 macrophages with atorvastatin, dose dependently (1–10 μm) stimulated cholesterol efflux to apolipoprotein AI (apoAI, 10–60%, p < 0.05) and high density lipoprotein (HDL3) (2–50%, p < 0.05), despite a significant decrease in cholesterol synthesis (2–90%). Atorvastatin also increased ABCA1 and ABCG1 mRNA abundance (30 and 35%, p < 0.05). Addition of mevalonate, GGPP or farnesyl pyrophosphate completely blocked the statin-induced increase in ABCA1 expression and apoAI-mediated cholesterol efflux. A role for RhoA was established, because two inhibitors of Rho protein activity, a geranylgeranyl transferase inhibitor and C3 exoenzyme, increased cholesterol efflux to apoAI (20–35%, p < 0.05), and macrophage expression of dominant-negative RhoA enhanced cholesterol efflux to apoAI (20%, p < 0.05). In addition, atorvastatin increased the RhoA levels in the cytosol fraction and decreased the membrane localization of RhoA. Atorvastatin treatment activated peroxisome proliferator activated receptor γ and increased LXR-mediated gene expression suggesting that atorvastatin induces cholesterol efflux through a molecular cascade involving inhibition of RhoA signaling, leading to increased peroxisome proliferator activated receptor γ activity, enhanced LXR activation, increased ABCA1 expression, and cholesterol efflux. Finally, statin treatment inhibited cholesteryl ester accumulation in macrophages challenged with atherogenic hypertriglyceridemic very low density lipoproteins indicating that statins can regulate foam cell formation.

scholarly journals Altered PPARγ Expression Promotes Myelin-Induced Foam Cell Formation in Macrophages in Multiple Sclerosis

2020 ◽  
Vol 21 (23) ◽  
pp. 9329
Author(s):  
Elien Wouters ◽  
Elien Grajchen ◽  
Winde Jorissen ◽  
Tess Dierckx ◽  
Suzan Wetzels ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Mononuclear Cells ◽  
Foam Cell ◽  
Cell Formation ◽  
Autoimmune Disorder ◽  
Foam Cell Formation ◽  
Peroxisome Proliferator ◽  
Peripheral Blood Mononuclear ◽  
Peroxisome Proliferator Activated Receptors ◽  
Pparγ Expression

Macrophages play a crucial role during the pathogenesis of multiple sclerosis (MS), a neuroinflammatory autoimmune disorder of the central nervous system. Important regulators of the metabolic and inflammatory phenotype of macrophages are liver X receptors (LXRs) and peroxisome proliferator-activated receptors (PPARs). Previously, it has been reported that PPARγ expression is decreased in peripheral blood mononuclear cells of MS patients. The goal of the present study was to determine to what extent PPARγ, as well as the closely related nuclear receptors PPARα and β and LXRα and β, are differentially expressed in monocytes from MS patients and how this change in expression affects the function of monocyte-derived macrophages. We demonstrate that monocytes of relapsing-remitting MS patients display a marked decrease in PPARγ expression, while the expression of PPARα and LXRα/β is not altered. Interestingly, exposure of monocyte-derived macrophages from healthy donors to MS-associated proinflammatory cytokines mimicked this reduction in PPARγ expression. While a reduced PPARγ expression did not affect the inflammatory and phagocytic properties of myelin-loaded macrophages, it did impact myelin processing by increasing the intracellular cholesterol load of myelin-phagocytosing macrophages. Collectively, our findings indicate that an inflammation-induced reduction in PPARγ expression promotes myelin-induced foam cell formation in macrophages in MS.

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