Modulation of cellular membrane properties as a potential therapeutic strategy to counter lipointoxication in obstructive pulmonary diseases
| Autor: | Amélie Bacle, Laurie-Anne Payet, Clarisse Vandebrouck, Thierry Ferreira, Frédéric Becq, Reynald Helye, Anne Cantereau, Romain Ferru-Clément, Christophe Jayle, Linette Kadri |
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| Přispěvatelé: | Laboratoire Coopératif Thanaplast-Carbios, Ecologie et biologie des interactions (EBI), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS)-Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Signalisation et Transports Ioniques Membranaires (STIM), Université de Poitiers-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Université de Poitiers-Université de Tours-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2018 |
| Předmět: |
Adult
Male 0301 basic medicine Cystic Fibrosis [SDV]Life Sciences [q-bio] Primary Cell Culture Cell Bronchi Oleic Acids Respiratory Mucosa Molecular Dynamics Simulation Cell Line Pulmonary Disease Chronic Obstructive 03 medical and health sciences Organelle medicine Humans Computer Simulation Mannitol Secretion Interleukin 8 Molecular Biology Phospholipids Aged Chemistry Endoplasmic reticulum Cell Membrane Fatty Acids Epithelial Cells Middle Aged Epithelium 3. Good health Cell biology 030104 developmental biology medicine.anatomical_structure Apoptosis Molecular Medicine Female Intracellular |
| Zdroj: | Biochimica et Biophysica Acta-Molecular Basis of Disease Biochimica et Biophysica Acta-Molecular Basis of Disease, Elsevier, 2018, 1864, pp.3069-3084. ⟨10.1016/j.bbadis.2018.06.021⟩ |
| ISSN: | 0925-4439 |
| DOI: | 10.1016/j.bbadis.2018.06.021 |
| Popis: | International audience; Maintaining the equilibrium between saturated and unsaturated fatty acids within membrane phospholipids (PLs) is crucial to sustain the optimal membrane biophysical properties, compatible with selective organellebased processes. Lipointoxication is a pathological condition under which saturated PLs tend to accumulate within the cell at the expense of unsaturated species, with major impacts on organelle function. Here, we show that human bronchial epithelial cells extracted from lungs of patients with Obstructive Pulmonary Diseases (OPDs), i. e. Cystic Fibrosis (CF) individuals and Smokers, display a characteristic lipointoxication signature, with excessive amounts of saturated PLs. Reconstitution of this signature in cellulo and in silico revealed that such an imbalance results in altered membrane properties and in a dramatic disorganization of the intracellular network of bronchial epithelial cells, in a process which can account for several OPD traits. Such features include Endoplasmic Reticulum-stress, constitutive IL8 secretion, bronchoconstriction and, ultimately, epithelial cell death by apoptosis. We also demonstrate that a recently-identified lipid-like molecule, which has been shown to behave as a "membrane-reshaper", counters all the lipointoxication hallmarks tested. Altogether, these insights highlight the modulation of membrane properties as a potential new strategy to heal and prevent highly detrimental symptoms associated with OPDs. |
| Databáze: | OpenAIRE |
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