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P62 Regulates resveratrol-mediated Fas/Cav-1 complex formation and transition from autophagy to apoptosis
Resveratrol is a potential polyphenol drug used in cancer treatment. We examined the relationship between autophagy and apoptosis in RSV-treated non-small lung adenocarcinoma A549 cells. Resveratrol treatment increased autophagy and autophagy-mediated degradation of P62. Immunocytochemistry revealed...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4359255/ https://www.ncbi.nlm.nih.gov/pubmed/25596736 |
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author | Zhang, Jun Ma, Ke Qi, Tingting Wei, Xiaoning Zhang, Qing Li, Guanwu Chiu, Jen-Fu |
author_facet | Zhang, Jun Ma, Ke Qi, Tingting Wei, Xiaoning Zhang, Qing Li, Guanwu Chiu, Jen-Fu |
author_sort | Zhang, Jun |
collection | PubMed |
description | Resveratrol is a potential polyphenol drug used in cancer treatment. We examined the relationship between autophagy and apoptosis in RSV-treated non-small lung adenocarcinoma A549 cells. Resveratrol treatment increased autophagy and autophagy-mediated degradation of P62. Immunocytochemistry revealed P62 co-localized with Fas/Cav-1 complexes, known to induce apoptosis. However, siRNA-mediated P62 downregulation enhanced formation of Fas/Cav-1 complexes, suggesting that P62 inhibited Fas/Cav-1 complex formation. Fas/Cav-1 complexes triggered caspase-8 activation and cleavage of Beclin-1, releasing a C-terminal Beclin-1 peptide that translocated to the mitochondria and initiate apoptosis. Inhibition of autophagy by siRNA-mediated repression of Beclin-1 also blocked RSV-induced apoptosis, showing a dependence of apoptosis on autophagy. P62 knockdown by siRNA accelerated the activation of caspase-8 and initiate apoptosis, while Cav-1 knockdown inhibited apoptosis, but increased autophagy. Inhibition of autophagy by 3-MA prevented both P62 degradation and induction of apoptosis, whereas inhibition of apoptosis by z-IETD-FMK or z-DEVD-FMK enhanced both P62 induction and autophagic cell death. In conclusion, P62 links resveratrol-induced autophagy to apoptosis. P62 blocks apoptosis by inhibiting Fas/Cav-1 complex formation, but RSV-induced autophagic degradation of P62 enables formation of Fas/Cav-1 complexes which then activate caspase-8-mediated Beclin-1 cleavage, resulting in translocation of the Beclin-1 C-terminal fragment to the mitochondria to initiate apoptosis. |
format | Online Article Text |
id | pubmed-4359255 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-43592552015-03-27 P62 Regulates resveratrol-mediated Fas/Cav-1 complex formation and transition from autophagy to apoptosis Zhang, Jun Ma, Ke Qi, Tingting Wei, Xiaoning Zhang, Qing Li, Guanwu Chiu, Jen-Fu Oncotarget Research Paper Resveratrol is a potential polyphenol drug used in cancer treatment. We examined the relationship between autophagy and apoptosis in RSV-treated non-small lung adenocarcinoma A549 cells. Resveratrol treatment increased autophagy and autophagy-mediated degradation of P62. Immunocytochemistry revealed P62 co-localized with Fas/Cav-1 complexes, known to induce apoptosis. However, siRNA-mediated P62 downregulation enhanced formation of Fas/Cav-1 complexes, suggesting that P62 inhibited Fas/Cav-1 complex formation. Fas/Cav-1 complexes triggered caspase-8 activation and cleavage of Beclin-1, releasing a C-terminal Beclin-1 peptide that translocated to the mitochondria and initiate apoptosis. Inhibition of autophagy by siRNA-mediated repression of Beclin-1 also blocked RSV-induced apoptosis, showing a dependence of apoptosis on autophagy. P62 knockdown by siRNA accelerated the activation of caspase-8 and initiate apoptosis, while Cav-1 knockdown inhibited apoptosis, but increased autophagy. Inhibition of autophagy by 3-MA prevented both P62 degradation and induction of apoptosis, whereas inhibition of apoptosis by z-IETD-FMK or z-DEVD-FMK enhanced both P62 induction and autophagic cell death. In conclusion, P62 links resveratrol-induced autophagy to apoptosis. P62 blocks apoptosis by inhibiting Fas/Cav-1 complex formation, but RSV-induced autophagic degradation of P62 enables formation of Fas/Cav-1 complexes which then activate caspase-8-mediated Beclin-1 cleavage, resulting in translocation of the Beclin-1 C-terminal fragment to the mitochondria to initiate apoptosis. Impact Journals LLC 2014-11-29 /pmc/articles/PMC4359255/ /pubmed/25596736 Text en Copyright: © 2015 Zhang et al. https://creativecommons.org/licenses/by/2.5/This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Zhang, Jun Ma, Ke Qi, Tingting Wei, Xiaoning Zhang, Qing Li, Guanwu Chiu, Jen-Fu P62 Regulates resveratrol-mediated Fas/Cav-1 complex formation and transition from autophagy to apoptosis |
title | P62 Regulates resveratrol-mediated Fas/Cav-1 complex formation and transition from autophagy to apoptosis |
title_full | P62 Regulates resveratrol-mediated Fas/Cav-1 complex formation and transition from autophagy to apoptosis |
title_fullStr | P62 Regulates resveratrol-mediated Fas/Cav-1 complex formation and transition from autophagy to apoptosis |
title_full_unstemmed | P62 Regulates resveratrol-mediated Fas/Cav-1 complex formation and transition from autophagy to apoptosis |
title_short | P62 Regulates resveratrol-mediated Fas/Cav-1 complex formation and transition from autophagy to apoptosis |
title_sort | p62 regulates resveratrol-mediated fas/cav-1 complex formation and transition from autophagy to apoptosis |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4359255/ https://www.ncbi.nlm.nih.gov/pubmed/25596736 |
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