Serum-induced arachidonic acid release and prostaglandin biosynthesis are potentiated by oxygenated sterols in NRK 49F cells

Lahoua, Z.; Astruc, M.; Paulet, A. Crastes de

doi:10.1016/0005-2760(88)90225-1

Cited by 23 publications

(3 citation statements)

References 30 publications

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“…These effects appear to be related to phenotypic changes of the cells [12]. We propose that activated LXRs by oxysterols in response to cellular sterol loading could stimulate strongly IL-1β-induced sPLA 2 gene expression before contributing to the extended production of pro-inflammatory mediators [47]. Among them, PGE2 (prostaglandin E2) and PGF2 modify cellular functions by increasing vascular permeability and decreasing vascular tone [48].…”

Section: Discussionmentioning

confidence: 99%

Oxysterol and 9-cis-retinoic acid stimulate the group IIA secretory phospholipase A2 gene in rat smooth-muscle cells

Antonio

Janvier

Brouillet

et al. 2003

Biochemical Journal

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The inflammation that occurs during rheumatoid arthritis or atherosclerosis is characterized by the release of large amounts of sPLA(2) (group IIA secretory phospholipase A(2)). We have shown previously that the sPLA(2) promoter in SMC (smooth-muscle cells) is activated by interleukin-1beta and cAMP-signalling pathways, through the interplay of multiple transcription factors [Antonio, Brouillet, Janvier, Monne, Bereziat, Andreani, and Raymondjean (2002) Biochem. J. 368, 415-424]. In the present study, we have investigated the regulation of sPLA(2) gene expression in rat aortic SMCs by oxysterols. We found that oxysterol ligands that bind to the LXR (liver X receptor), including 25-HC (25-hydroxycholesterol) and 22( R )-HC, cause the accumulation of sPLA(2) mRNA and an increased enzyme activity. Transient transfection experiments demonstrated that the sPLA(2) promoter is synergistically activated by 22( R )-HC in combination with 9- cis -retinoic acid, a ligand for the LXR heterodimeric partner RXR (retinoid X receptor). Promoter activity was also increased in a sterol-responsive fashion when cells were co-transfected with LXRalpha/RXRalpha or LXRbeta/RXRalpha. Mutagenesis studies and gel mobility-shift assays revealed that LXR/RXR heterodimers regulate sPLA(2) transcription directly, by interacting with a degenerated LXRE (LXR response element) at position [-421/-406] of the sPLA(2) promoter. Chromatin immunoprecipitation revealed the in vivo occupancy of LXR on the sPLA(2) promoter. In addition, the orphan nuclear receptor LRH-1 (liver receptor homologue-1) potentiated the sterol-dependent regulation of the sPLA(2) promoter by binding to an identified promoter element (TCAAGGCTG). Finally, we have demonstrated that oxysterols act independent of interleukin-1beta and cAMP pathways to activate the sPLA(2) promoter. In the present study, we have identified a new pathway activating sPLA(2) gene expression in SMCs.

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Section: Discussionmentioning

confidence: 99%

Oxysterol and 9-cis-retinoic acid stimulate the group IIA secretory phospholipase A2 gene in rat smooth-muscle cells

Antonio

Janvier

Brouillet

et al. 2003

Biochemical Journal

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“…In fact, dietary COPs increase the production of PGI 2 in the aorta. It has been reported that COPs influence arachidonic acid release from cell membrane phospholipids and cyclooxygenase activity in vitro [35,36]. The imbalance in the eicosanoid level is associated with various homeostasis-related disturbances concerning lipid metabolism.…”

Section: Discussionmentioning

confidence: 99%

Absorption of Dietary Cholesterol Oxidation Products and Their Downstream Metabolic Effects Are Reduced by Dietary Apple Polyphenols

Ogino

Osada

Nakamura

et al. 2007

Lipids

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Exogenous and endogenous cholesterol oxidation products (COPs) perturb various metabolic processes, and thereby they may induce various homeostasis-related disorders. Here, we observed that procyanidin-rich dietary apple polyphenol (APP) from unripe apples alleviates the perturbation of lipid metabolism by decreasing the exogenous COP levels in rats. Dietary COPs may be the greatest source of COPs found in the human body. Rats (4 weeks of age) were fed AIN-purified diets containing 0.3% COPs supplemented with 0.5 or 2.5% APP for 3 weeks. Dietary APP alleviated the growth inhibition action of the exogenous COPs. The modulations of the liver lipid profile by COPs remained unchanged. However, serum total cholesterol, high-density lipoprotein cholesterol, and triglyceride levels increased following the intake of dietary APP. Further, dietary APP inhibited the increase in lipid peroxide levels in the liver and serum by COPs. The activity of hepatic Delta6 desaturase was lowered by dietary APP in a dose-dependent manner, although exogenous COPs generally increased the activity of this enzyme. In keeping with this observation, Delta6 desaturation indices in the phospholipids and cholesteryl esters of the liver and serum lipids were lower in the APP-fed groups than those in the control group. Dietary APP also promoted the excretion of exogenous COPs, cholesterol, and acidic steroids in feces. Therefore, the inhibition of intestinal absorption of COPs may partly contribute to the alleviation of the perturbation of lipid metabolism and lipid peroxidation levels. Thus, APP may be an important removal agent of exogenous toxic material such as COPs contained in processed or fast foods.

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“…It has been proposed that oxygenated sterols might be involved in signal transduction. Lahoua et al (534) observed that several oxysterols potentiated the effect of FCS in the stimulation of arachidonic acid release in NRK 49F cells. 7␣-OH-Chol, 7␤-OH-Chol, and 25-OH-Chol were active in this respect, whereas 7-keto-Chol and Chol had no effect at various concentrations including the highest levels tested (25 M for 7-keto-Chol and 26 M for Chol).…”

Section: U Oxysterols and Signal Transductionmentioning

confidence: 99%

Oxysterols: Modulators of Cholesterol Metabolism and Other Processes

Schroepfer

2000

Physiological Reviews

877

687

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Oxygenated derivatives of cholesterol (oxysterols) present a remarkably diverse profile of biological activities, including effects on sphingolipid metabolism, platelet aggregation, apoptosis, and protein prenylation. The most notable oxysterol activities center around the regulation of cholesterol homeostasis, which appears to be controlled in part by a complex series of interactions of oxysterol ligands with various receptors, such as the oxysterol binding protein, the cellular nucleic acid binding protein, the sterol regulatory element binding protein, the LXR nuclear orphan receptors, and the low-density lipoprotein receptor. Identification of the endogenous oxysterol ligands and elucidation of their enzymatic origins are topics of active investigation. Except for 24, 25-epoxysterols, most oxysterols arise from cholesterol by autoxidation or by specific microsomal or mitochondrial oxidations, usually involving cytochrome P-450 species. Oxysterols are variously metabolized to esters, bile acids, steroid hormones, cholesterol, or other sterols through pathways that may differ according to the type of cell and mode of experimentation (in vitro, in vivo, cell culture). Reliable measurements of oxysterol levels and activities are hampered by low physiological concentrations (approximately 0.01-0.1 microM plasma) relative to cholesterol (approximately 5,000 microM) and by the susceptibility of cholesterol to autoxidation, which produces artifactual oxysterols that may also have potent activities. Reports describing the occurrence and levels of oxysterols in plasma, low-density lipoproteins, various tissues, and food products include many unrealistic data resulting from inattention to autoxidation and to limitations of the analytical methodology. Because of the widespread lack of appreciation for the technical difficulties involved in oxysterol research, a rigorous evaluation of the chromatographic and spectroscopic methods used in the isolation, characterization, and quantitation of oxysterols has been included. This review comprises a detailed and critical assessment of current knowledge regarding the formation, occurrence, metabolism, regulatory properties, and other activities of oxysterols in mammalian systems.

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Serum-induced arachidonic acid release and prostaglandin biosynthesis are potentiated by oxygenated sterols in NRK 49F cells

Cited by 23 publications

References 30 publications

Oxysterol and 9-cis-retinoic acid stimulate the group IIA secretory phospholipase A2 gene in rat smooth-muscle cells

Oxysterol and 9-cis-retinoic acid stimulate the group IIA secretory phospholipase A2 gene in rat smooth-muscle cells

Absorption of Dietary Cholesterol Oxidation Products and Their Downstream Metabolic Effects Are Reduced by Dietary Apple Polyphenols

Oxysterols: Modulators of Cholesterol Metabolism and Other Processes

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