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Targeting Protective Autophagy Exacerbates UV-Triggered Apoptotic Cell Death
Autophagy is activated by various stresses, including DNA damage, and previous studies of DNA damage-induced autophagy have focused on the response to chemotherapeutic drugs, ionizing radiation, and reactive oxygen species. In this study, we investigated the biological significance of autophagic res...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Molecular Diversity Preservation International (MDPI)
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3269747/ https://www.ncbi.nlm.nih.gov/pubmed/22312313 http://dx.doi.org/10.3390/ijms13011209 |
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author | Chen, Li-Hsin Chu, Pei-Ming Lee, Yi-Jang Tu, Pang-Hsien Chi, Chin-Wen Lee, Hsin-Chen Chiou, Shih-Hwa |
author_facet | Chen, Li-Hsin Chu, Pei-Ming Lee, Yi-Jang Tu, Pang-Hsien Chi, Chin-Wen Lee, Hsin-Chen Chiou, Shih-Hwa |
author_sort | Chen, Li-Hsin |
collection | PubMed |
description | Autophagy is activated by various stresses, including DNA damage, and previous studies of DNA damage-induced autophagy have focused on the response to chemotherapeutic drugs, ionizing radiation, and reactive oxygen species. In this study, we investigated the biological significance of autophagic response to ultraviolet (UV) irradiation in A549 and H1299 cells. Our results indicated that UV induces on-rate autophagic flux in these cells. Autophagy inhibition resulting from the knockdown of beclin-1 and Atg5 reduced cell viability and enhanced apoptosis. Moreover, we found that ATR phosphorylation was accompanied by microtubule-associated protein 1 light chain 3B II (LC3B-II) expression during the early phases following UV irradiation, which is a well-established inducer of ATR. Knocking down ATR further attenuated the reduction in LC3B-II at early stages in response to UV treatment. Despite the potential role of ATR in autophagic response, reduced ATR expression does not affect autophagy induction during late phases (24 and 48 h after UV treatment). The result is consistent with the reduced ATR phosphorylation at the same time points and suggests that autophagic response at this stage is activated via a distinct pathway. In conclusion, this study demonstrated that autophagy acts as a cytoprotective mechanism against UV-induced apoptosis and that autophagy induction accompanied with apoptosis at late stages is independent of ATR activation. |
format | Online Article Text |
id | pubmed-3269747 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Molecular Diversity Preservation International (MDPI) |
record_format | MEDLINE/PubMed |
spelling | pubmed-32697472012-02-06 Targeting Protective Autophagy Exacerbates UV-Triggered Apoptotic Cell Death Chen, Li-Hsin Chu, Pei-Ming Lee, Yi-Jang Tu, Pang-Hsien Chi, Chin-Wen Lee, Hsin-Chen Chiou, Shih-Hwa Int J Mol Sci Article Autophagy is activated by various stresses, including DNA damage, and previous studies of DNA damage-induced autophagy have focused on the response to chemotherapeutic drugs, ionizing radiation, and reactive oxygen species. In this study, we investigated the biological significance of autophagic response to ultraviolet (UV) irradiation in A549 and H1299 cells. Our results indicated that UV induces on-rate autophagic flux in these cells. Autophagy inhibition resulting from the knockdown of beclin-1 and Atg5 reduced cell viability and enhanced apoptosis. Moreover, we found that ATR phosphorylation was accompanied by microtubule-associated protein 1 light chain 3B II (LC3B-II) expression during the early phases following UV irradiation, which is a well-established inducer of ATR. Knocking down ATR further attenuated the reduction in LC3B-II at early stages in response to UV treatment. Despite the potential role of ATR in autophagic response, reduced ATR expression does not affect autophagy induction during late phases (24 and 48 h after UV treatment). The result is consistent with the reduced ATR phosphorylation at the same time points and suggests that autophagic response at this stage is activated via a distinct pathway. In conclusion, this study demonstrated that autophagy acts as a cytoprotective mechanism against UV-induced apoptosis and that autophagy induction accompanied with apoptosis at late stages is independent of ATR activation. Molecular Diversity Preservation International (MDPI) 2012-01-20 /pmc/articles/PMC3269747/ /pubmed/22312313 http://dx.doi.org/10.3390/ijms13011209 Text en © 2012 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0 This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/). |
spellingShingle | Article Chen, Li-Hsin Chu, Pei-Ming Lee, Yi-Jang Tu, Pang-Hsien Chi, Chin-Wen Lee, Hsin-Chen Chiou, Shih-Hwa Targeting Protective Autophagy Exacerbates UV-Triggered Apoptotic Cell Death |
title | Targeting Protective Autophagy Exacerbates UV-Triggered Apoptotic Cell Death |
title_full | Targeting Protective Autophagy Exacerbates UV-Triggered Apoptotic Cell Death |
title_fullStr | Targeting Protective Autophagy Exacerbates UV-Triggered Apoptotic Cell Death |
title_full_unstemmed | Targeting Protective Autophagy Exacerbates UV-Triggered Apoptotic Cell Death |
title_short | Targeting Protective Autophagy Exacerbates UV-Triggered Apoptotic Cell Death |
title_sort | targeting protective autophagy exacerbates uv-triggered apoptotic cell death |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3269747/ https://www.ncbi.nlm.nih.gov/pubmed/22312313 http://dx.doi.org/10.3390/ijms13011209 |
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