Induction of heme oxygenase-1, biliverdin reductase and H-ferritin in lung macrophage in smokers with primary spontaneous pneumothorax: role of HIF-1alpha
| Autor: | Anne Boutten, Delphine Goven, Marcel Bonay, Joëlle Marchal-Somme, Paul Soler, Jorge Boczkowski, Véronique Leçon-Malas |
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| Přispěvatelé: | Physiopathologie et Epidemiologie de l'Insuffisance Respiratoire, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de biochimie A, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Physiologie-Explorations Fonctionnelles, Funding was provided by Subvention de Recherche en Pneumologie, Appel d'Offre Automne 2008, Société de Pneumologie de Langue Française (SPLF), http://www.splf.org/s, Guellaen, Georges |
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Biopsy
lcsh:Medicine medicine.disease_cause chemistry.chemical_compound 0302 clinical medicine lcsh:Science Heme Respiratory Medicine Lung 0303 health sciences Multidisciplinary biology medicine.diagnostic_test Biliverdin reductase Smoking Pneumothorax Blood Proteins Pathology/Molecular Pathology Cell Hypoxia 3. Good health medicine.anatomical_structure 030220 oncology & carcinogenesis Enzyme Induction Proteoglycans medicine.symptom Research Article Oxidoreductases Acting on CH-CH Group Donors NF-E2-Related Factor 2 Antigens Differentiation Myelomonocytic Eosinophil Major Basic Protein Cell Line 03 medical and health sciences Western blot Antigens CD medicine [SDV.BBM] Life Sciences [q-bio]/Biochemistry Molecular Biology Humans [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Gene Silencing RNA Messenger 030304 developmental biology Macrophages lcsh:R Hypoxia (medical) Hypoxia-Inducible Factor 1 alpha Subunit Molecular biology eye diseases Ferritin Heme oxygenase Pathology/Pathophysiology Oxygen Oxidative Stress chemistry Gene Expression Regulation Apoferritins biology.protein lcsh:Q Reactive Oxygen Species Oxidative stress Heme Oxygenase-1 |
| Zdroj: | PLoS ONE PLoS ONE, Public Library of Science, 2010, 5 (5), pp.e10886. ⟨10.1371/journal.pone.0010886⟩ PLoS ONE, Vol 5, Iss 5, p e10886 (2010) |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0010886⟩ |
| Popis: | International audience; BACKGROUND: Few data concern the pathophysiology of primary spontaneous pneumothorax (PSP), which is associated with alveolar hypoxia/reoxygenation. This study tested the hypothesis that PSP is associated with oxidative stress in lung macrophages. We analysed expression of the oxidative stress marker 4-HNE; the antioxidant and anti-inflammatory proteins heme oxygenase-1 (HO-1), biliverdin reductase (BVR) and heavy chain of ferritin (H-ferritin); and the transcription factors controlling their expression Nrf2 and HIF-1alpha, in lung samples from smoker and nonsmoker patients with PSP (PSP-S and PSP-NS), cigarette smoke being a risk factor of recurrence of the disease. METHODOLOGY/PRINCIPAL FINDINGS: mRNA was assessed by RT-PCR and proteins by western blot, immunohistochemistry and confocal laser analysis. 4-HNE, HO-1, BVR and H-ferritin were increased in macrophages from PSP-S as compared to PSP-NS and controls (C). HO-1 increase was associated with increased expression of HIF-1alpha mRNA and protein in alveolar macrophages in PSP-S patients, whereas Nrf2 was not modified. To understand the regulation of HO-1, BVR and H-ferritin, THP-1 macrophages were exposed to conditions mimicking conditions in C, PSP-S and PSP-NS patients: cigarette smoke condensate (CS) or air exposure followed or not by hypoxia/reoxygenation. Silencing RNA experiments confirmed that HIF-1alpha nuclear translocation was responsible for HO-1, BVR and H-ferritin induction mediated by CS and hypoxia/reoxygenation. CONCLUSIONS/SIGNIFICANCE: PSP in smokers is associated with lung macrophage oxidative stress. The response to this condition involves HIF-1alpha-mediated induction of HO-1, BVR and H-ferritin. |
| Databáze: | OpenAIRE |
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