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Hyperosmotic stress stimulates autophagy via polycystin-2

Various intracellular mechanisms are activated in response to stress, leading to adaptation or death. Autophagy, an intracellular process that promotes lysosomal degradation of proteins, is an adaptive response to several types of stress. Osmotic stress occurs under both physiological and pathologic...

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Autores principales: Peña-Oyarzun, Daniel, Troncoso, Rodrigo, Kretschmar, Catalina, Hernando, Cecilia, Budini, Mauricio, Morselli, Eugenia, Lavandero, Sergio, Criollo, Alfredo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5593539/
https://www.ncbi.nlm.nih.gov/pubmed/28915568
http://dx.doi.org/10.18632/oncotarget.18995
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author Peña-Oyarzun, Daniel
Troncoso, Rodrigo
Kretschmar, Catalina
Hernando, Cecilia
Budini, Mauricio
Morselli, Eugenia
Lavandero, Sergio
Criollo, Alfredo
author_facet Peña-Oyarzun, Daniel
Troncoso, Rodrigo
Kretschmar, Catalina
Hernando, Cecilia
Budini, Mauricio
Morselli, Eugenia
Lavandero, Sergio
Criollo, Alfredo
author_sort Peña-Oyarzun, Daniel
collection PubMed
description Various intracellular mechanisms are activated in response to stress, leading to adaptation or death. Autophagy, an intracellular process that promotes lysosomal degradation of proteins, is an adaptive response to several types of stress. Osmotic stress occurs under both physiological and pathological conditions, provoking mechanical stress and activating various osmoadaptive mechanisms. Polycystin-2 (PC2), a membrane protein of the polycystin family, is a mechanical sensor capable of activating the cell signaling pathways required for cell adaptation and survival. Here we show that hyperosmotic stress provoked by treatment with hyperosmolar concentrations of sorbitol or mannitol induces autophagy in HeLa and HCT116 cell lines. In addition, we show that mTOR and AMPK, two stress sensor proteins involved modulating autophagy, are downregulated and upregulated, respectively, when cells are subjected to hyperosmotic stress. Finally, our findings show that PC2 is required to promote hyperosmotic stress-induced autophagy. Downregulation of PC2 prevents inhibition of hyperosmotic stress-induced mTOR pathway activation. In conclusion, our data provide new insight into the role of PC2 as a mechanosensor that modulates autophagy under hyperosmotic stress conditions.
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spelling pubmed-55935392017-09-14 Hyperosmotic stress stimulates autophagy via polycystin-2 Peña-Oyarzun, Daniel Troncoso, Rodrigo Kretschmar, Catalina Hernando, Cecilia Budini, Mauricio Morselli, Eugenia Lavandero, Sergio Criollo, Alfredo Oncotarget Research Paper: Autophagy and Cell Death Various intracellular mechanisms are activated in response to stress, leading to adaptation or death. Autophagy, an intracellular process that promotes lysosomal degradation of proteins, is an adaptive response to several types of stress. Osmotic stress occurs under both physiological and pathological conditions, provoking mechanical stress and activating various osmoadaptive mechanisms. Polycystin-2 (PC2), a membrane protein of the polycystin family, is a mechanical sensor capable of activating the cell signaling pathways required for cell adaptation and survival. Here we show that hyperosmotic stress provoked by treatment with hyperosmolar concentrations of sorbitol or mannitol induces autophagy in HeLa and HCT116 cell lines. In addition, we show that mTOR and AMPK, two stress sensor proteins involved modulating autophagy, are downregulated and upregulated, respectively, when cells are subjected to hyperosmotic stress. Finally, our findings show that PC2 is required to promote hyperosmotic stress-induced autophagy. Downregulation of PC2 prevents inhibition of hyperosmotic stress-induced mTOR pathway activation. In conclusion, our data provide new insight into the role of PC2 as a mechanosensor that modulates autophagy under hyperosmotic stress conditions. Impact Journals LLC 2017-07-05 /pmc/articles/PMC5593539/ /pubmed/28915568 http://dx.doi.org/10.18632/oncotarget.18995 Text en Copyright: © 2017 Peña-Oyarzun et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Research Paper: Autophagy and Cell Death
Peña-Oyarzun, Daniel
Troncoso, Rodrigo
Kretschmar, Catalina
Hernando, Cecilia
Budini, Mauricio
Morselli, Eugenia
Lavandero, Sergio
Criollo, Alfredo
Hyperosmotic stress stimulates autophagy via polycystin-2
title Hyperosmotic stress stimulates autophagy via polycystin-2
title_full Hyperosmotic stress stimulates autophagy via polycystin-2
title_fullStr Hyperosmotic stress stimulates autophagy via polycystin-2
title_full_unstemmed Hyperosmotic stress stimulates autophagy via polycystin-2
title_short Hyperosmotic stress stimulates autophagy via polycystin-2
title_sort hyperosmotic stress stimulates autophagy via polycystin-2
topic Research Paper: Autophagy and Cell Death
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5593539/
https://www.ncbi.nlm.nih.gov/pubmed/28915568
http://dx.doi.org/10.18632/oncotarget.18995
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