Oxidized Low-Density Lipoproteins Trigger Endoplasmic Reticulum Stress in Vascular Cells
| Autor: | Sanson, Marie, Augé, Nathalie, Vindis, Cécile, Muller, Carole, Bando, Yoshio, Thiers, Jean-Claude, Marachet, Marie-Agnè, s, Žarković, Kamelija, Sawa, Yoshiki, Salvayre, Robert, Nè, gre-Salvayre, Anne |
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| Přispěvatelé: | Simon, Marie Francoise, Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Régulations cellulaires: lipidoses et atherosclerose, IFR 31 Louis Bugnard (IFR 31), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Anatomy, Asahikawa Medical College, Département de biologie vasculaire, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biochimie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Division of Pathology, University of Zagreb, Department of Surgery, Osaka University [Osaka], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Laboratoire de Biochimie [Purpan], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], University of Osaka |
| Rok vydání: | 2009 |
| Předmět: |
MESH: Lipoproteins
LDL Physiology [SDV]Life Sciences [q-bio] Apoptosis Endoplasmic Reticulum MESH: Atherosclerosis 0302 clinical medicine MESH: Endothelial Cells MESH: Proteins Enzyme Inhibitors MESH: Stress Physiological Endoplasmic Reticulum Chaperone BiP Ketocholesterols 0303 health sciences [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology biology Kinase MESH: Ketocholesterols Free Radical Scavengers Cell biology Lipoproteins LDL [SDV] Life Sciences [q-bio] Biochemistry MESH: Enzyme Inhibitors 030220 oncology & carcinogenesis lipids (amino acids peptides and proteins) Cardiology and Cardiovascular Medicine MESH: Oxygen XBP1 KDEL Cysteine Proteinase Inhibitors In Vitro Techniques MESH: Cysteine Proteinase Inhibitors 03 medical and health sciences MESH: Acetylcysteine ER stress apoptosis ORP150 oxidized LDL atherosclerosis Lipid oxidation Stress Physiological MESH: Endoplasmic Reticulum Humans HSP70 Heat-Shock Proteins 030304 developmental biology Aldehydes MESH: Humans ATF6 MESH: Apoptosis Endoplasmic reticulum JNK Mitogen-Activated Protein Kinases MESH: Biological Markers Endothelial Cells Proteins MESH: JNK Mitogen-Activated Protein Kinases Atherosclerosis Acetylcysteine Oxygen Chaperone (protein) MESH: Free Radical Scavengers biology.protein Unfolded protein response MESH: Aldehydes Biomarkers [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology |
| Zdroj: | Circulation Research Circulation Research, 2009, 104 (3), pp.328-36. ⟨10.1161/CIRCRESAHA.108.183749⟩ Circulation Research, American Heart Association, 2009, 104 (3), pp.328-36. ⟨10.1161/CIRCRESAHA.108.183749⟩ |
| ISSN: | 1524-4571 0009-7330 |
| Popis: | Oxidized low-density lipoproteins (oxLDLs) trigger various biological responses potentially involved in atherogenesis. Disturbing endoplasmic reticulum (ER) function results in ER stress and unfolded protein response, which tends to restore ER homeostasis but switches to apoptosis when ER stress is prolonged. We aimed to investigate whether ER stress is induced by oxLDLs and can be prevented by the ER-associated chaperone ORP150 (150-kDa oxygen-regulated protein). oxLDLs and the lipid oxidation products 7-ketocholesterol and 4-hydroxynonenal induce ER stress in human endothelial cells (HMEC-1), characterized by the activation of ER stress sensors (phosphorylation of Ire1α and PERK, nuclear translocation of ATF6) and of their subsequent pathways (eukaryotic initiation factor 2α phosphorylation, expression of XBP1/spliced XBP1, CHOP, and KDEL chaperones GRP78, GRP94, ORP150). ER stress was inhibited by the antioxidant N -acetylcysteine. In advanced atherosclerotic lesions, phospho-Ire1α, KDEL, and ORP150 staining were localized in lipid-rich areas with 4-hydroxynonenal adducts and CD68-positive macrophagic cells. By comparison, staining for 4-hydroxynonenal, phospho-Ire1α, KDEL, and ORP were faint and more diffuse in intimal hyperplasia. ER stress takes part in the apoptotic effect of oxLDLs, through the Ire1α/c-Jun N-terminal kinase pathway, as assessed by the protective effect of specific small interfering RNAs and c-Jun N-terminal kinase inhibitor. Forced expression of the chaperone ORP150 reduced both oxLDL-induced ER stress and apoptosis. ER stress markers and ORP150 chaperone are expressed in areas containing oxLDLs in atherosclerotic lesions and are induced by oxLDLs and oxidized lipids in cultured cells. The forced expression of ORP150 highlights its new protective role against oxLDL-induced ER stress and subsequent apoptosis. |
| Databáze: | OpenAIRE |
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