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Regulation of macroautophagy in amiodarone‐induced pulmonary fibrosis
Amiodarone (AD) is an iodinated benzofuran derivative, especially known for its antiarrhythmic properties. It exerts serious side‐effects even in patients receiving low doses. AD is well‐known to induce apoptosis of type II alveolar epithelial cells (AECII), a mechanism that has been suggested to pl...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4939895/ https://www.ncbi.nlm.nih.gov/pubmed/27499909 http://dx.doi.org/10.1002/cjp2.20 |
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author | Mahavadi, Poornima Knudsen, Lars Venkatesan, Shalini Henneke, Ingrid Hegermann, Jan Wrede, Christoph Ochs, Matthias Ahuja, Saket Chillappagari, Shashi Ruppert, Clemens Seeger, Werner Korfei, Martina Guenther, Andreas |
author_facet | Mahavadi, Poornima Knudsen, Lars Venkatesan, Shalini Henneke, Ingrid Hegermann, Jan Wrede, Christoph Ochs, Matthias Ahuja, Saket Chillappagari, Shashi Ruppert, Clemens Seeger, Werner Korfei, Martina Guenther, Andreas |
author_sort | Mahavadi, Poornima |
collection | PubMed |
description | Amiodarone (AD) is an iodinated benzofuran derivative, especially known for its antiarrhythmic properties. It exerts serious side‐effects even in patients receiving low doses. AD is well‐known to induce apoptosis of type II alveolar epithelial cells (AECII), a mechanism that has been suggested to play an important role in AD‐induced lung fibrosis. The precise molecular mechanisms underlying this disease are, however, still unclear. Because of its amphiphilic nature, AD becomes enriched in the lysosomal compartments, affecting the general functions of these organelles. Hence, in this study, we aimed to assess the role of autophagy, a lysosome‐dependent homeostasis mechanism, in driving AECII apoptosis in response to AD. In vitro, AD‐treated MLE12 and primary AECII cells showed increased proSP‐C and LC3B positive vacuolar structures and underwent LC3B‐dependent apoptosis. In addition, AD‐induced autophagosome‐lysosome fusion and increased autophagy flux were observed. In vivo, in C57BL/6 mice, LC3B was localised at the limiting membrane of lamellar bodies, which were closely connected to the autophagosomal structures in AECIIs. Our data suggest that AD causes activation of macroautophagy in AECIIs and extensive autophagy‐dependent apoptosis of alveolar epithelial cells. Targeting the autophagy pathway may therefore represent an attractive treatment modality in AD‐induced lung fibrosis. |
format | Online Article Text |
id | pubmed-4939895 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-49398952016-08-05 Regulation of macroautophagy in amiodarone‐induced pulmonary fibrosis Mahavadi, Poornima Knudsen, Lars Venkatesan, Shalini Henneke, Ingrid Hegermann, Jan Wrede, Christoph Ochs, Matthias Ahuja, Saket Chillappagari, Shashi Ruppert, Clemens Seeger, Werner Korfei, Martina Guenther, Andreas J Pathol Clin Res Original Articles Amiodarone (AD) is an iodinated benzofuran derivative, especially known for its antiarrhythmic properties. It exerts serious side‐effects even in patients receiving low doses. AD is well‐known to induce apoptosis of type II alveolar epithelial cells (AECII), a mechanism that has been suggested to play an important role in AD‐induced lung fibrosis. The precise molecular mechanisms underlying this disease are, however, still unclear. Because of its amphiphilic nature, AD becomes enriched in the lysosomal compartments, affecting the general functions of these organelles. Hence, in this study, we aimed to assess the role of autophagy, a lysosome‐dependent homeostasis mechanism, in driving AECII apoptosis in response to AD. In vitro, AD‐treated MLE12 and primary AECII cells showed increased proSP‐C and LC3B positive vacuolar structures and underwent LC3B‐dependent apoptosis. In addition, AD‐induced autophagosome‐lysosome fusion and increased autophagy flux were observed. In vivo, in C57BL/6 mice, LC3B was localised at the limiting membrane of lamellar bodies, which were closely connected to the autophagosomal structures in AECIIs. Our data suggest that AD causes activation of macroautophagy in AECIIs and extensive autophagy‐dependent apoptosis of alveolar epithelial cells. Targeting the autophagy pathway may therefore represent an attractive treatment modality in AD‐induced lung fibrosis. John Wiley and Sons Inc. 2015-06-03 /pmc/articles/PMC4939895/ /pubmed/27499909 http://dx.doi.org/10.1002/cjp2.20 Text en © 2015 John Wiley and Sons Ltd and The Pathological Society of Great Britain and Ireland This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Original Articles Mahavadi, Poornima Knudsen, Lars Venkatesan, Shalini Henneke, Ingrid Hegermann, Jan Wrede, Christoph Ochs, Matthias Ahuja, Saket Chillappagari, Shashi Ruppert, Clemens Seeger, Werner Korfei, Martina Guenther, Andreas Regulation of macroautophagy in amiodarone‐induced pulmonary fibrosis |
title | Regulation of macroautophagy in amiodarone‐induced pulmonary fibrosis |
title_full | Regulation of macroautophagy in amiodarone‐induced pulmonary fibrosis |
title_fullStr | Regulation of macroautophagy in amiodarone‐induced pulmonary fibrosis |
title_full_unstemmed | Regulation of macroautophagy in amiodarone‐induced pulmonary fibrosis |
title_short | Regulation of macroautophagy in amiodarone‐induced pulmonary fibrosis |
title_sort | regulation of macroautophagy in amiodarone‐induced pulmonary fibrosis |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4939895/ https://www.ncbi.nlm.nih.gov/pubmed/27499909 http://dx.doi.org/10.1002/cjp2.20 |
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