Dual Promoter Structure of Mouse and Human Fatty Acid Translocase/CD36 Genes and Unique Transcriptional Activation by Peroxisome Proliferator-activated Receptor α and γ Ligands

Sato, Osamu; Kuriki, Chikako; Fukui, Yuka; Motojima, Kiyoto

doi:10.1074/jbc.m110158200

Cited by 144 publications

(134 citation statements)

References 48 publications

Supporting

Mentioning

128

Contrasting

Order By: Relevance

“…As detailed above, PPAR-c was reported to upregulate expression of scavenger receptor CD36 [11,106,107] and downregulate SR-A in macrophages [108]. PPAR-c was also reported to induce oxLDL receptor-1 in adipocytes resulting in increased uptake of the lipoprotein [109].…”

Section: Uptake Of Modified Ldl By Pattern Recognition Receptorsmentioning

confidence: 89%

Nuclear receptors in macrophages: A link between metabolism and inflammation

Szántó

Röszer

2007

FEBS Letters

View full text Add to dashboard Cite

Subclinical inflammation is a candidate etiological factor in the pathogenesis of metabolic syndrome and in the progression of atherosclerosis. A central role for activated macrophages has been elucidated recently as important regulators of the inflammatory process in atherosclerosis. Macrophage differentiation and function can be modulated by a class of transcription factors termed nuclear receptors. These are activated by intermediary products of basic metabolic processes. In this review the contribution of peroxisome proliferator-activated receptors and liver X receptors to macrophage functions in inflammation and lipid metabolism will be discussed in light of their roles in macrophages during atherosclerosis.In the past decade much effort has been made to understand the mechanisms how lipids are handled by macrophages and how inflammation could promote the atherogenic process. Here, we also provide an overview of these two fields.

show abstract

Section: Uptake Of Modified Ldl By Pattern Recognition Receptorsmentioning

confidence: 89%

Nuclear receptors in macrophages: A link between metabolism and inflammation

Szántó

Röszer

2007

FEBS Letters

View full text Add to dashboard Cite

show abstract

“…ND indicates not detected; C18:3n-6/C18:2n-6, ⌬6 desaturase index; C20:4n-6/C20:3n-6, ⌬5 desaturase index. PPAR␥ in liver and adipose tissue, respectively, 39,40 and by PPAR␦ in macrophages 41 and skeletal muscle, 42 underscoring the complexity of the PPAR system in which the responses to a certain ligand may differ between different cell types and tissues. Several studies have suggested antiinflammatory effects after PPAR␣ 14,15 and PPAR␥ activation, 16 although the antiinflammatory properties of PPAR␥ are more controversial.…”

Section: Discussionmentioning

confidence: 99%

Tetradecylselenoacetic Acid, a PPAR Ligand With Antioxidant, Antiinflammatory, and Hypolipidemic Properties

Dyrøy

Røst

Pettersen

et al. 2007

ATVB

View full text Add to dashboard Cite

Objective-Antioxidants protect against oxidative stress and inflammation, which, in combination with hyperlipidemia, are important mediators of atherogenesis. Here we present a selenium-substituted fatty acid, tetradecylselenoacetic acid (TSA), which is hypothesized to have antioxidant, antiinflammatory, and hypolipidemic properties. Methods and Results-We show that TSA exerts antioxidant properties by delaying the onset of oxidation of human low density lipoprotein (LDL), by reducing the uptake of oxidized LDL in murine macrophages, and by increasing the mRNA level of superoxide dismutase in rat liver. TSA also showed antiinflammatory effects by suppressing the release of interleukin (IL)-2 and -4, and by increasing the release of IL-10 in human blood leukocytes. In addition, TSA decreased the plasma triacylglycerol level and increased the mitochondrial fatty acid ␤-oxidation in rat liver. In pigs, TSA seemed to reduce coronary artery intimal thickening after percutaneous coronary intervention. In HepG2 cells TSA activated all peroxisome proliferator-activated receptors (PPARs) in a dose-dependent manner. Conclusions-Our data suggest that TSA exert potent antioxidant, antiinflammatory, and hypolipidemic properties, potentially involving PPAR-related mechanisms. Based on these effects, it is tempting to hypothesize that TSA could be an interesting antiatherogenic approach to atherosclerotic disorders. A therosclerosis is regarded as an inflammatory disorder of the vascular wall, where multiple factors contribute to a persistent and self-perpetual inflammation within the atherosclerotic lesions. [1][2][3][4][5] There is also a consensus that atherosclerosis represents a state of elevated oxidative stress characterized by lipid and protein oxidation in the vascular wall. 6 Enhanced inflammation and oxidative stress seem to represent a vicious circle in atherogenesis, and therapeutic options directed against these processes seems like a reasonable approach in the management of atherosclerotic disorders.We have previously shown that tetradecylthioacetic acid (TTA), a modified fatty acid with a sulfur atom in the third position of the carbon backbone, promotes mitochondrial and peroxisomal proliferation, and decreases serum lipid levels in animal models. 7-9 TTA also shows antioxidant effects in vitro 10 and encompasses antiinflammatory properties in human leukocytes. 11 The pleiotropic effects of TTA seem to involve activation of peroxisome proliferator-activated receptors (PPARs), 12,13 which are receptors that serves as an important link between lipid metabolism and inflammation. 14 -17 Tetradecylselenoacetic acid (TSA) is a novel fatty acid which in comparison to TTA has a selenium atom instead of a sulfur atom in third position of the carbon backbone. As with TTA, 18 this modification makes TSA resistant to fatty acid ␤-oxidation. A previous in vitro study has demonstrated that TSA is a stronger antioxidant than TTA. 19 Based on these findings and its relation to TTA, we hypothesized that TSA also exerts poten...

show abstract

“…The basal expression of several genes is dominantly regulated in a tissue-specific manner, and not induced by a PPAR ligand alone even if that tissue abundantly expresses PPARs (Sato et al, 2002). This tissue specific PPAR action can be explained by two possibilities: i. the responsive gene is generally and dominantly repressed and PPAR/RXR alone cannot activate transcription without a tissue specific enhancing factor; ii.…”

Section: Insidementioning

confidence: 99%