Caveolin mRNA levels are up-regulated by free cholesterol and down-regulated by oxysterols in fibroblast monolayers

Fielding, Christopher J.; Bist, Anita; Fielding, Phoebe E.

doi:10.1073/pnas.94.8.3753

Cited by 235 publications

(192 citation statements)

References 39 publications

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“…That oxide does not inhibit nitric oxide synthesis and does not act on estrogen receptors, but has a cytotoxic effect on endothelial cells 47,48 . Fielding et al 29 reported that cholesterol oxides reduce caveolin mRNA, the transportation of free cholesterol to cell surface, and free cholesterol efflux. Caveolae are probable intermediates of free cholesterol efflux via HDL 29 .…”

Section: Discussionmentioning

confidence: 99%

“…Fielding et al 29 reported that cholesterol oxides reduce caveolin mRNA, the transportation of free cholesterol to cell surface, and free cholesterol efflux. Caveolae are probable intermediates of free cholesterol efflux via HDL 29 . The presence of oxysterols in HDL reduces the capacity of that lipoprotein to stimulate cholesterol efflux 32 .…”

Section: Discussionmentioning

confidence: 99%

“…Caveolin mRNA (protein present in the caveolae and that interacts with eNOS) is up-regulated when the uptake of free cholesterol from LDL to the cell is increased. The regulation of the efflux of free cholesterol via the caveolar path is mediated by caveolin mRNA 29 . Evidence indicates that the increase in caveolin regulation in cells exposed to high levels of LDL-cholesterol results directly from an increase in the transcription of the eNOS gene induced by the higher cellular content of cholesterol 30 .…”

Section: Total Oxysterolsmentioning

confidence: 99%

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Lipid peroxidation and nitric oxide inactivation in postmenopausal women

Pereira

Bertolami

Faludi

et al. 2003

Arq. Bras. Cardiol.

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Original ArticleCardiovascular diseases are less prevalent in premenopausal women and in those receiving hormone replacement therapy as compared with postmenopausal women and men 1 . This protective effect is attributed to estrogens, and one of the mechanisms of action may be related to the metabolism of plasma lipoproteins 2 .Estrogens reduce LDL-cholesterol and increase HDLcholesterol 3 . However, these changes in lipid profile only contribute to approximately 25% of the protective effect of estrogens 4 . Other potential mechanisms of action of estrogens may include protection against LDL oxidation 5 , reduction in lipoprotein(a), potentiation of fibrinolysis 6 , and increase in insulin sensitivity. In the arteries, estrogens improve vasodilating function, decrease calcification, secretion of cell adhesion molecules (E-selectin, ICAM-1, and VCAM-1), and formation of atherosclerotic lesions 7 .Direct action of estrogens on the arterial wall has also been demonstrated. The administration of estrogens for prolonged periods inhibits the deposition of cholesterol in the arteries and thickening of the intima in monkeys and rabbits fed an atherogenic diet 8 . However, the mechanisms determining the direct effects of estrogens on the arterial wall have not been completely elucidated. The hemodynamic effects may be partially measured by the activity of estrogens on the synthesis of endothelial nitric oxide 9 . Estrogens have been suggested to possibly improve endothelial function and decrease the risks of atherosclerosis in premenopausal women. Nitric oxide has its bioactivity reduced in postmenopausal women. However, it is not clear whether this occurs due to its lower production by nitric oxide synthase, or whether nitric oxide is inactivated by reaction with the superoxide radical also generated by endothelial cells, forming the peroxynitrite anion (ONOO -), which is a strong oxidizing agent.Peroxynitrite is decomposed into other reactive oxygen species ( fig. 1) 10 and reacts with tyrosine residues of proteins to form nitrotyrosine 11 . Although little is known NOx, nitrotyrosine, COx, CE 18:2 -OOH, and PC-OOH were higher in the postmenopausal period (33.8±22.3 µM; 230±130 nM; 55±19 ng/µL; 17±8.7 nM; 2775±460 nM, respectively) Objective -To assess the effect of endogenous estrogens on the bioavailability of nitric oxide (·NO) and in the formation of lipid peroxidation products in pre-and postmenopausal women. Methods -NOx and S-nitrosothiols were determined by gaseous phase chemiluminescence, nitrotyrosine was determined by ELISA, COx (cholesterol oxides) by gas chromatography, and cholesteryl linoleate hydroperoxides (CE 18:2 -OOH), trilinolein (TG 18:2 -OOH), and phospholipids (PC-OOH) by HPLC in samples of plasma. Results -The concentrations of

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Total Oxysterolsmentioning

confidence: 99%

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Lipid peroxidation and nitric oxide inactivation in postmenopausal women

Pereira

Bertolami

Faludi

et al. 2003

Arq. Bras. Cardiol.

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“…For example, the mitogen-activated protein kinase pathway extracellular signalregulated kinase (ERK) has been shown to control caveolin-1 expression at the transcriptional level in NIH 3T3 cells (10), whereas activation of Src family kinases transcriptionally decreases caveolin-1 expression (2). In addition, caveolin-1 transcription is up-regulated by sterol regulatory elementbinding protein-1 in response to free cholesterol, which results in caveolae formation and increased cholesterol efflux (12,13). Conversely, high density lipoprotein exposure reduces caveolin-1 expression and prevents the uptake of oxidized cholesterol (14).…”

mentioning

confidence: 99%

The Tetraspan Protein EMP2 Regulates Expression of Caveolin-1

Forbes¹,

Wadehra

Mareninov³

et al. 2007

Journal of Biological Chemistry

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Caveolin-1 is the primary component of caveolae and functions in a variety of intracellular activities, including membrane trafficking and signal transduction. EMP2 (epithelial membrane protein 2) is a tetraspan protein recently identified as a novel regulator of caveolin-1 expression. In this study, we analyzed the mechanism of EMP2-mediated caveolin-1 regulation. In NIH 3T3 cells and in the human retinal pigment epithelium cell line (ARPE-19), EMP2 regulates caveolin-1 transcription and more substantially its protein levels. EMP2-mediated down-regulation of caveolin-1 does not affect caveolin-1 translational efficiency, phosphorylation, or proteasome-mediated degradation. Analysis of caveolin-1 protein half-life indicates the EMP2-mediated loss of caveolin-1 occurs rapidly. Protease inhibition and laser confocal microscopy associates this fate with specific intracellular compartmentalization, including early lysosomal delivery. These findings elucidate a new mechanism of caveolin-1 regulation and define an additional role for EMP2 as a key regulator of cell membrane composition.

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“…Although specific experiments have to be performed to understand the precise effects of oxysterols in HSA secretion, several in vitro experiments have already shown that oxysterols can reduce protein expression and mRNA levels in cultured cells. 46,47 Different transcription factors have been shown to be involved in the sterol-mediated regulation of genes involved in cholesterol homeostasis. Most extensive studies have been carried out on the sterol regulatory element binding proteins 1 and 2, which are responsible for the sterol-mediated suppression of the LDL receptor, 3-hydroxy-3-methylglutaryl coenzyme A synthase, and fatty acid synthase genes.…”

Section: Discussionmentioning

confidence: 99%

Involvement of Oxysterols and Lysophosphatidylcholine in the Oxidized LDL–Induced Impairment of Serum Albumin Synthesis by HEPG2 Cells

Bourdon

Loreau

Davignon

et al. 2000

ATVB

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Abstract-Oxidized low density lipoproteins (Ox-LDLs) are increasingly thought to be a key element in atherogenesis. We have previously reported that serum albumin has important antioxidant properties and that a reduced synthesis of albumin may represent a crucial point in the overall antioxidant defense. In the present work, we aimed at determining whether Ox-LDL could modulate albumin synthesis in cultured human hepatocytes (HepG2 cells). With the use of enzyme immunoassay and radiolabeled leucine incorporation followed by specific immunoprecipitation, Ox-LDL was found to lead to a dose-dependent decrease in albumin secretion. Moreover, the protein synthesis and mRNA levels were decreased in the presence of Ox-LDL, as assessed by Northern blot analysis. Because oxysterols and lysophospholipids are key components of Ox-LDL, we tested the effects of oxysterols (7-ketocholesterol and 25-hydroxycholesterol) and lysophosphatidylcholine on albumin secretion and expression. In our experimental conditions, we found that incubations with oxysterols or lysophosphatidylcholine at pathophysiological concentrations similar to those measured in Ox-LDLs reproduced the above-mentioned inhibitory effects on albumin synthesis. On the basis of our in vitro data, we propose that this newly described biological effect of Ox-LDL might partly explain the findings of epidemiological studies indicating that reduced levels of serum albumin are associated with increased mortality. (Arterioscler Thromb Vasc

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Caveolin mRNA levels are up-regulated by free cholesterol and down-regulated by oxysterols in fibroblast monolayers

Cited by 235 publications

References 39 publications

Lipid peroxidation and nitric oxide inactivation in postmenopausal women

Lipid peroxidation and nitric oxide inactivation in postmenopausal women

The Tetraspan Protein EMP2 Regulates Expression of Caveolin-1

Involvement of Oxysterols and Lysophosphatidylcholine in the Oxidized LDL–Induced Impairment of Serum Albumin Synthesis by HEPG2 Cells

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