Oxidized Low-Density Lipoproteins Trigger Endoplasmic Reticulum Stress in Vascular Cells

Sanson, Marie; Augé, Nathalie; Vindis, Cécile; Muller, C.; Bandô, Yoshio; Thiers, Jean-Claude; Marachet, Marie-Agnès; Žarković, Kamelija; Sawa, Yoshiki; Salvayre, Robert; Nègre‐Salvayre, Anne

doi:10.1161/circresaha.108.183749

Cited by 163 publications

(143 citation statements)

References 58 publications

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“…We recently reported that oxLDLs induce the activation of the three ER stress sensors as assessed by the phosphorylation of IRE1a, PERK and of the PERK substrate eIF2a and by the nuclear translocation of ATF6. 9 In the present study, we investigated the effect of HDLs on the activation of these ER stress sensors elicited by oxLDLs stimulation. Our data show that pre-treatment of HMEC-1 cells with HDLs, followed by coincubation with oxLDLs significantly reduced the time-dependent phosphorylation of IRE1a and eIF2a (Figure 1a and b).…”

Section: Resultsmentioning

confidence: 99%

“…3,4 The proapoptotic effects of oxLDLs are mediated through a complex sequence of signaling events that lead to the activation of several caspase-dependent or caspase-independent apoptotic pathways 2,5,6 Previously, we reported that treatment of human vascular endothelial and smooth muscle cells with oxLDLs or 7-ketocholesterol (a major oxysterol in oxLDLs) causes an increase in cytosolic Ca 2 þ through TRPC1 channels that triggers a proteolytic cascade involving Ca 2 þ -dependent calpains, Bid cleavage and cytochrome c release, leading finally to caspase-3 activation and apoptosis. [7][8][9] Recently, we have reported that oxLDLs induced the unfolded protein response (UPR) and triggered endoplasmic reticulum (ER) stress. 9 ER is a sensor for cellular stress, as it rapidly detects changes in cell homeostasis, and responds by triggering UPR via the activation of ER transmembrane sensors, PERK and IRE1a (two serine/threonine kinases), and ATF6 which acts as a transcription factor.…”

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confidence: 99%

“…[7][8][9] Recently, we have reported that oxLDLs induced the unfolded protein response (UPR) and triggered endoplasmic reticulum (ER) stress. 9 ER is a sensor for cellular stress, as it rapidly detects changes in cell homeostasis, and responds by triggering UPR via the activation of ER transmembrane sensors, PERK and IRE1a (two serine/threonine kinases), and ATF6 which acts as a transcription factor. The UPR results in a temporary downregulation of protein translation, an upregulation of ER chaperones and folding machinery, and the expression and activation of ER-associated degradation (ERAD).…”

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confidence: 99%

“…Prolonged ER stress switches toward apoptotic cell death via the activation of downstream signals like CHOP, JNK and members of the Bcl-2 family. 10,11 ER stress markers (phosphorylation of IRE1a and expression of KDEL motifbearing proteins) in human advanced atherosclerotic lesions, 9 raising the question of the possible role of ER stress in the stability/unstability of atherosclerotic plaques, as this new adaptative response may determine the fate of cells to survive or die. 11 Autophagy is involved in the turnover of cellular macromolecules, 12 which could mediate, in part, the removal of ER-accumulated protein, via the ER-associated chaperone GRP78/Bip, 13 and the release of Ca 2 þ from the ER into the cytosol.…”

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HDLs inhibit endoplasmic reticulum stress and autophagic response induced by oxidized LDLs

et al. 2010

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The apoptotic effect of oxidized LDLs (oxLDLs) is mediated through a complex sequence of signaling events involving a deregulation of the cytosolic Ca 2 þ homeostasis. OxLDLs also trigger ER stress that may lead to cellular dysfunction and apoptosis, through the activation of the IRE1a/c-Jun N-terminal kinase pathway. Moreover, ER stress and oxidized lipids have been shown to trigger autophagy. The antiatherogenic high-density lipoproteins (HDLs) display protective effects against oxLDLs toxicity. To more deeply investigate the mechanisms mediating the protective effects of HDLs, we examined whether ER stress and autophagy were implicated in oxLDLs-induced apoptosis and whether HDLs prevented these stress processes. We report that, in human endothelial cells, HDLs prevent the oxLDL-induced activation of the ER stress sensors IRE1a, eIF2a and ATF6 and subsequent activation of the proapoptotic mediators JNK and CHOP. OxLDLs also trigger the activation of autophagy, as assessed by LC3 processing and Beclin-1 expression. The autophagic process is independent of the proapoptotic arms of ER stress, but Beclin-1 contributes to PS exposure and subsequent phagocytosis of oxLDLs exposed cells. Induction of autophagy and PS exposure by oxLDLs is prevented by HDLs. Finally, the cytosolic Ca 2 þ deregulation triggered by oxLDLs is a common signaling pathway that mediates ER stress-induced cell death and autophagy, all these events being blocked by HDLs.

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HDLs inhibit endoplasmic reticulum stress and autophagic response induced by oxidized LDLs

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“…It has long been known that disruption of intracellular calcium homeostasis is one of the primary processes in the early development of cell injury [1][2][3] [19,[24][25][26][27][28]. In summary, ER homeostasis is a fragile equilibrium, which can be modulated by dysregulation of calcium or oxidative/reductive balance, features previously associated with oxidative stress.…”

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confidence: 99%

Endoplasmic reticulum calcium release potentiates the ER stress and cell death caused by an oxidative stress in MCF-7 cells

Dejeans

Tajeddine

Beck

et al. 2010

Biochemical Pharmacology

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Please cite this article as: Dejeans N, Tajeddine N, Beck R, Verrax J, Taper H, Gailly P, Calderon PB, Endoplasmic reticulum calcium release potentiates the ER stress and cell death caused by an oxidative stress in MCF-7 cells, Biochemical Pharmacology (2008), doi:10.1016/j.bcp.2009 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A c c e p t e d M a n u s c r i p t 2 ABSTRACTIncrease in cytosolic calcium concentration ([Ca 2+ ] c ), release of endoplasmic reticulum (ER) calcium ([Ca 2+ ] er ) and ER stress have been proposed to be involved in oxidative toxicity.Nevertheless, their relative involvements in the processes leading to cell death are not well defined. In this study, we investigated whether oxidative stress generated during ascorbatedriven menadione redox cycling (Asc/Men) could trigger these three events, and, if so, A c c e p t e d M a n u s c r i p t 3 IntroductionIt has long been known that disruption of intracellular calcium homeostasis is one of the primary processes in the early development of cell injury [1][2][3] [19,[24][25][26][27][28]. In summary, ER homeostasis is a fragile equilibrium, which can be modulated by dysregulation of calcium or oxidative/reductive balance, features previously associated with oxidative stress. However, studies of the links between these factors are scarce.We and others have shown that the association of ascorbate and menadione is an H 2 O 2 -generating system that results in necrosis-like cell death in a wide variety of cancer cell types [29][30][31][32][33][34][35] including MCF-7 cells (a human breast derived cell line), and that loss of calcium homeostasis appeared to be a major factor in the cytotoxicity [36]. The aim of the present study was to investigate the role of disruption of calcium homeostasis and a potential involvement of ER stress in the mechanisms leading to cancer cell death from an oxidative Materials and methods ChemicalsMenadione sodium bisulfite (Men), sodium ascorbate ( Cell Culture and TreatmentsThe MCF-7 cell line was a gift from Dr. F. Brasseur (Ludwig Institute for Cancer Research, LICR-Brussels). The cells were cultured in DMEM (Dulbecco's modified eagle medium, (Gibco BRL, Life Technologies, Merelbeke, BE)) supplemented with 10% fetal calf serum, penicillin (10 000 U/ml), streptomycin (10 mg/ml) and 1.2% glutamine. The cultures were maintained at a density of about 50x10³ cells/cm². The medium was changed at 48-72 h intervals. All cultures were maintained at 37°C in 95% air/5% CO2 with 100% humidity. minutes before the addition of ascorbate and menadione. Cells were incubated with TG or iodoacetate at concentration...

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Endoplasmic reticulum stress and endothelial dysfunction

2014

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Prolonged perturbation of the endoplasmic reticulum (ER) leads to ER stress and unfolded protein response (UPR) and contributes to the pathogenesis of various chronic disorders. This review focuses on the role of ER stress and UPR in endothelial cells and the relevance of these processes to vascular diseases. Chronic activation of ER stress and UPR pathways in endothelial cells leads to increased oxidative stress and inflammation, and often results in cell death. Because endothelial cells play a pivotal role in maintaining vascular homeostasis, various pathological conditions interfering with this homeostasis including homocysteinemia, hyperlipidimia, high glucose, insulin resistance, disturbed blood flow, and oxidative stress can lead to endothelial dysfunction in part through the activation of ER stress. We discuss recently discovered aspects of the role of ER stress/UPR in those pathological conditions. We also summarize recent findings implicating ER stress and UPR in systemic hypertension, as well as pulmonary arterial hypertension (PAH). Finally, this review will highlight a novel role of UPR mediators in the process of angiogenesis.

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Oxidized Low-Density Lipoproteins Trigger Endoplasmic Reticulum Stress in Vascular Cells

Cited by 163 publications

References 58 publications

HDLs inhibit endoplasmic reticulum stress and autophagic response induced by oxidized LDLs

HDLs inhibit endoplasmic reticulum stress and autophagic response induced by oxidized LDLs

Endoplasmic reticulum calcium release potentiates the ER stress and cell death caused by an oxidative stress in MCF-7 cells

Endoplasmic reticulum stress and endothelial dysfunction

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