Trans-arachidonic acids generated during nitrative stress induce a thrombospondin-1-dependent microvascular degeneration
| Autor: | Gregor Andelfinger, Chantal J. Boisvert, Elsa Kermorvant-Duchemin, Sonia Brault, Huy Ong, J Russel Falck, Pedro D'Orléans-Juste, Florian Sennlaub, Stéphane Germain, Pierre Hardy, Michael Balazy, Amna Kooli, Fernand Gobeil, Tang Zhu, Kavita Jain, Mirna Sirinyan, Sylvain Chemtob |
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| Přispěvatelé: | Department of Pediatrics, Ophthalmology and Pharmacology, Hôpital Sainte-Justine, Physiopathologie des Maladies Oculaires : Innovations Therapeutiques, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR58-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Pharmacology and Therapeutics [Montréal], McGill University = Université McGill [Montréal, Canada], Pathologie vasculaire et endocrinologie rénale - Chaire de médecine expérimentale (INSERM U36), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM), Faculty of Pharmacy [Montréal, QC, Canada], Université de Montréal (UdeM), Department of Pharmacology, Université de Sherbrooke (UdeS), New York Medical College (NYMC), Department of Biochemistry, The University of Texas Health Science Center at Houston (UTHealth), Sennlaub, Florian, CHU Sainte Justine [Montréal] |
| Jazyk: | angličtina |
| Rok vydání: | 2005 |
| Předmět: |
MESH: Oxidation-Reduction
MESH: Nitroarginine Sus scrofa Tetrazolium Salts Apoptosis MESH: Rats Sprague-Dawley MESH: Animals Newborn Neovascularization Rats Sprague-Dawley Thrombospondin 1 chemistry.chemical_compound 0302 clinical medicine MESH: Microcirculation MESH: Animals Cells Cultured MESH: Glutathione 0303 health sciences MESH: Oxidative Stress Reverse Transcriptase Polymerase Chain Reaction MESH: Retina General Medicine 3. Good health Cell biology Biochemistry MESH: Metalloporphyrins MESH: Isoenzymes Arachidonic acid MESH: Nitric Oxide Synthase [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] medicine.symptom MESH: Oxygen MESH: Rats Cell Survival Blotting Western MESH: Malondialdehyde Ischemia Neovascularization Physiologic Arachidonic Acids Biology Nitric Oxide General Biochemistry Genetics and Molecular Biology Article Nitric oxide 03 medical and health sciences Downregulation and upregulation In vivo medicine In Situ Nick-End Labeling Animals [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] 030304 developmental biology DNA Primers MESH: Antioxidants Endothelial Cells Retinal Vessels medicine.disease Rats Thiazoles chemistry Gene Expression Regulation MESH: Nitric Oxide 030217 neurology & neurosurgery Ex vivo Diabetic Angiopathies |
| Zdroj: | Nature Medicine Nature Medicine, Nature Publishing Group, 2005, 11 (12), pp.1339-45. ⟨10.1038/nm1336⟩ Nature Medicine, 2005, 11 (12), pp.1339-45. ⟨10.1038/nm1336⟩ |
| ISSN: | 1078-8956 1744-7933 |
| DOI: | 10.1038/nm1336⟩ |
| Popis: | E K-D and F S contributed equally to this work; Nitrative stress has an important role in microvascular degeneration leading to ischemia in conditions such as diabetic retinopathy and retinopathy of prematurity. Thus far, mediators of nitrative stress have been poorly characterized. We recently described that trans-arachidonic acids are major products of NO(2)(*)-mediated isomerization of arachidonic acid within the cell membrane, but their biological relevance is unknown. Here we show that trans-arachidonic acids are generated in a model of retinal microangiopathy in vivo in a NO(*)-dependent manner. They induce a selective time- and concentration-dependent apoptosis of microvascular endothelial cells in vitro, and result in retinal microvascular degeneration ex vivo and in vivo. These effects are mediated by an upregulation of the antiangiogenic factor thrombospondin-1, independently of classical arachidonic acid metabolism. Our findings provide new insight into the molecular mechanisms of nitrative stress in microvascular injury and suggest new therapeutic avenues in the management of disorders involving nitrative stress, such as ischemic retinopathies and encephalopathies. |
| Databáze: | OpenAIRE |
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