| Cystic fibrosis: a disorder with defective autophagy. | |
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MedLine Citation:
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PMID: 21048426 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The accumulation of misfolded and/or ubiquitinated protein aggregates with a perturbation of autophagy has been described in several human pathologies. A sequestration of misfolded cystic: fibrosis transmembrane conductance regulator (CFTR) and cross-linked PPARγ has been observed in airway epithelia of cystic fibrosis (CF) patients. CF airways are also characterized by chronic inflammation, pro-oxidative environment and increased transglutaminase 2 (TG2) levels. We showed that defective CFTR drives autophagy inhibition through reactive oxygen species (ROS)-TG2- mediated aggresome sequestration of the Beclin 1 interactome. Rescuing Beclin 1 at the level of the endoplasmic reticulum and autophagy favors clearance of aggresomes, improves CFTR trafficking and ameliorates CF lung inflammation both in vitro and in vivo. Therefore, rescuing autophagy interrupts the vicious cycle linking defective CFTR and lung inflammation and may pave the way to the development of a novel class of drugs for the treatment of CF. |
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Authors:
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Alessandro Luciani; Valeria R Villella; Speranza Esposito; Nicola Brunetti-Pierri; Diego L Medina; Carmine Settembre; Manuela Gavina; Valeria Raia; Andrea Ballabio; Luigi Maiuri |
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Publication Detail:
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Type: Journal Article Date: 2011-01-01 |
Journal Detail:
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Title: Autophagy Volume: 7 ISSN: 1554-8635 ISO Abbreviation: Autophagy Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2010-11-30 Completed Date: 2011-03-21 Revised Date: 2012-02-28 |
Medline Journal Info:
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Nlm Unique ID: 101265188 Medline TA: Autophagy Country: United States |
Other Details:
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Languages: eng Pagination: 104-6 Citation Subset: IM |
Affiliation:
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European Institute for Research in Cystic Fibrosis, San Raffaele Scientific Institute, Milan, Italy. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Autophagy* Cystic Fibrosis / enzymology, pathology* Cystic Fibrosis Transmembrane Conductance Regulator / metabolism Endoplasmic Reticulum / metabolism, pathology Enzyme Activation GTP-Binding Proteins / metabolism Humans Mice Models, Biological Reactive Oxygen Species / metabolism Transglutaminases / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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TGM06S01//Telethon; TGM11S01//Telethon |
| Chemical | |
Reg. No./Substance:
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0/Reactive Oxygen Species; 126880-72-6/Cystic Fibrosis Transmembrane Conductance Regulator; EC 2.3.2.-/transglutaminase 2; EC 2.3.2.13/Transglutaminases; EC 3.6.1.-/GTP-Binding Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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