Oxygen-regulated protein-150 prevents calcium homeostasis deregulation and apoptosis induced by oxidized LDL in vascular cells
| Autor: | Cécile Vindis, Yoshio Bando, Anne Nègre-Salvayre, Ziad Mallat, Robert Salvayre, Yoshiki Sawa, Marie Sanson, Yves Glock, Jean-Claude Thiers, Hervé Rousseau, Cécile Ingueneau |
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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), Service Cardiologie [CHU Toulouse], Pôle Cardiovasculaire et Métabolique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Division of Cardiovascular Surgery, Department of Surgery, Osaka University [Osaka], Department of Functional Anatomy and Neuroscience, Asahikawa Medical College, Centre de Recherche Cardiovasculaire de Lariboisiere, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de cardiologie [Toulouse], Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse] |
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Carotid Artery Diseases
MESH: Lipoproteins LDL MESH: Boron Compounds Apoptosis Endoplasmic Reticulum MESH: Chelating Agents Antioxidants MESH: Atherosclerosis 0302 clinical medicine MESH: Macrocyclic Compounds Homeostasis MESH: Endothelial Cells MESH: Proteins Egtazic Acid Oxazoles Chelating Agents Calcium signaling 0303 health sciences Cytochrome c MESH: Oxazoles Calpain Cell biology Lipoproteins LDL MESH: Homeostasis MESH: Calcium RNA Interference lipids (amino acids peptides and proteins) Boron Compounds Programmed cell death Macrocyclic Compounds MESH: Egtazic Acid MESH: RNA Interference chemistry.chemical_element Caspase 3 Calcium Biology MESH: Calcium Signaling Cell Line 03 medical and health sciences MESH: Endoplasmic Reticulum [SDV.BBM] Life Sciences [q-bio]/Biochemistry Molecular Biology Humans HSP70 Heat-Shock Proteins [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Calcium Signaling Molecular Biology 030304 developmental biology Calcium metabolism MESH: Humans MESH: Carotid Artery Diseases MESH: Apoptosis MESH: Antioxidants Endothelial Cells Proteins Cell Biology Atherosclerosis MESH: Cell Line chemistry biology.protein 030217 neurology & neurosurgery |
| Zdroj: | Cell Death and Differentiation Cell Death and Differentiation, 2008, 15 (8), pp.1255-65. ⟨10.1038/cdd.2008.36⟩ Cell Death and Differentiation, Nature Publishing Group, 2008, 15 (8), pp.1255-65. ⟨10.1038/cdd.2008.36⟩ |
| ISSN: | 1350-9047 1476-5403 |
| Popis: | International audience; Oxidized LDLs (oxLDLs) induce apoptosis, which contributes to the pathogenesis of atherosclerosis. The 150 kDa oxygen-regulated protein (ORP150), an endoplasmic reticulum (ER)-resident chaperone, is upregulated by hypoxia and prevents ischemia-induced cell death. The aim of this work was to investigate whether and how ORP150 can prevent apoptosis induced by oxLDLs in vascular cells. OxLDLs induced ORP150 expression in the ER of human microvascular endothelial cell line (HMEC-1). ORP150 expression was blocked by antioxidants, by the permeant calcium chelator BAPTA-AM, and by inhibitors of the inositol-1,4,5 trisphosphate (IP3) receptors, 2-aminoethyl diphenylborinate (2-APB) and xestospongin C. ORP150 silencing by siRNA-enhanced oxLDL-induced apoptosis, while forced ORP150 expression increased the resistance of cells via an inhibition of the oxLDL-induced calcium rise, and of subsequent calpain activation, cytochrome c release, caspase 3 activation and apoptosis. A similar protective effect was achieved by BAPTA-AM, 2-APB and xestospongin C. Altogether, these data indicate that (i)ORP150 inhibits oxLDL-induced apoptosis by blocking calcium signaling and subsequent apoptosis, (ii)calcium released from ER stores through IP3 channels is involved in the oxLDL-induced calcium rise and apoptosis, and is inhibited by ORP150. Finally, ORP150 is expressed in advanced atherosclerotic lesions, where it may locally participate to reduce the apoptotic effect of oxLDLs and the subsequent risk of plaque rupture. |
| Databáze: | OpenAIRE |
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