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An interplay between UCP2 and ROS protects cells from high-salt-induced injury through autophagy stimulation
The mitochondrial uncoupling protein 2 (UCP2) plays a protective function in the vascular disease of both animal models and humans. UCP2 downregulation upon high-salt feeding favors vascular dysfunction in knock-out mice, and accelerates cerebrovascular and renal damage in the stroke-prone spontaneo...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8501098/ https://www.ncbi.nlm.nih.gov/pubmed/34625529 http://dx.doi.org/10.1038/s41419-021-04188-4 |
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author | Forte, Maurizio Bianchi, Franca Cotugno, Maria Marchitti, Simona Stanzione, Rosita Maglione, Vittorio Sciarretta, Sebastiano Valenti, Valentina Carnevale, Roberto Versaci, Francesco Frati, Giacomo Volpe, Massimo Rubattu, Speranza |
author_facet | Forte, Maurizio Bianchi, Franca Cotugno, Maria Marchitti, Simona Stanzione, Rosita Maglione, Vittorio Sciarretta, Sebastiano Valenti, Valentina Carnevale, Roberto Versaci, Francesco Frati, Giacomo Volpe, Massimo Rubattu, Speranza |
author_sort | Forte, Maurizio |
collection | PubMed |
description | The mitochondrial uncoupling protein 2 (UCP2) plays a protective function in the vascular disease of both animal models and humans. UCP2 downregulation upon high-salt feeding favors vascular dysfunction in knock-out mice, and accelerates cerebrovascular and renal damage in the stroke-prone spontaneously hypertensive rat. Overexpression of UCP2 counteracts the negative effects of high-salt feeding in both animal models. We tested in vitro the ability of UCP2 to stimulate autophagy and mitophagy as a mechanism mediating its protective effects upon high-salt exposure in endothelial and renal tubular cells. UCP2 silencing reduced autophagy and mitophagy, whereas the opposite was true upon UCP2 overexpression. High-salt exposure increased level of reactive oxygen species (ROS), UCP2, autophagy and autophagic flux in both endothelial and renal tubular cells. In contrast, high-salt was unable to induce autophagy and autophagic flux in UCP2-silenced cells, concomitantly with excessive ROS accumulation. The addition of an autophagy inducer, Tat-Beclin 1, rescued the viability of UCP2-silenced cells even when exposed to high-salt. In summary, UCP2 mediated the interaction between high-salt-induced oxidative stress and autophagy to preserve viability of both endothelial and renal tubular cells. In the presence of excessive ROS accumulation (achieved upon UCP2 silencing and high-salt exposure of silenced cells) autophagy was turned off. In this condition, an exogenous autophagy inducer rescued the cellular damage induced by excess ROS level. Our data confirm the protective role of UCP2 toward high-salt-induced vascular and renal injury, and they underscore the role of autophagy/mitophagy as a mechanism counteracting the high-salt-induced oxidative stress damage. |
format | Online Article Text |
id | pubmed-8501098 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-85010982021-10-22 An interplay between UCP2 and ROS protects cells from high-salt-induced injury through autophagy stimulation Forte, Maurizio Bianchi, Franca Cotugno, Maria Marchitti, Simona Stanzione, Rosita Maglione, Vittorio Sciarretta, Sebastiano Valenti, Valentina Carnevale, Roberto Versaci, Francesco Frati, Giacomo Volpe, Massimo Rubattu, Speranza Cell Death Dis Article The mitochondrial uncoupling protein 2 (UCP2) plays a protective function in the vascular disease of both animal models and humans. UCP2 downregulation upon high-salt feeding favors vascular dysfunction in knock-out mice, and accelerates cerebrovascular and renal damage in the stroke-prone spontaneously hypertensive rat. Overexpression of UCP2 counteracts the negative effects of high-salt feeding in both animal models. We tested in vitro the ability of UCP2 to stimulate autophagy and mitophagy as a mechanism mediating its protective effects upon high-salt exposure in endothelial and renal tubular cells. UCP2 silencing reduced autophagy and mitophagy, whereas the opposite was true upon UCP2 overexpression. High-salt exposure increased level of reactive oxygen species (ROS), UCP2, autophagy and autophagic flux in both endothelial and renal tubular cells. In contrast, high-salt was unable to induce autophagy and autophagic flux in UCP2-silenced cells, concomitantly with excessive ROS accumulation. The addition of an autophagy inducer, Tat-Beclin 1, rescued the viability of UCP2-silenced cells even when exposed to high-salt. In summary, UCP2 mediated the interaction between high-salt-induced oxidative stress and autophagy to preserve viability of both endothelial and renal tubular cells. In the presence of excessive ROS accumulation (achieved upon UCP2 silencing and high-salt exposure of silenced cells) autophagy was turned off. In this condition, an exogenous autophagy inducer rescued the cellular damage induced by excess ROS level. Our data confirm the protective role of UCP2 toward high-salt-induced vascular and renal injury, and they underscore the role of autophagy/mitophagy as a mechanism counteracting the high-salt-induced oxidative stress damage. Nature Publishing Group UK 2021-10-08 /pmc/articles/PMC8501098/ /pubmed/34625529 http://dx.doi.org/10.1038/s41419-021-04188-4 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Forte, Maurizio Bianchi, Franca Cotugno, Maria Marchitti, Simona Stanzione, Rosita Maglione, Vittorio Sciarretta, Sebastiano Valenti, Valentina Carnevale, Roberto Versaci, Francesco Frati, Giacomo Volpe, Massimo Rubattu, Speranza An interplay between UCP2 and ROS protects cells from high-salt-induced injury through autophagy stimulation |
title | An interplay between UCP2 and ROS protects cells from high-salt-induced injury through autophagy stimulation |
title_full | An interplay between UCP2 and ROS protects cells from high-salt-induced injury through autophagy stimulation |
title_fullStr | An interplay between UCP2 and ROS protects cells from high-salt-induced injury through autophagy stimulation |
title_full_unstemmed | An interplay between UCP2 and ROS protects cells from high-salt-induced injury through autophagy stimulation |
title_short | An interplay between UCP2 and ROS protects cells from high-salt-induced injury through autophagy stimulation |
title_sort | interplay between ucp2 and ros protects cells from high-salt-induced injury through autophagy stimulation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8501098/ https://www.ncbi.nlm.nih.gov/pubmed/34625529 http://dx.doi.org/10.1038/s41419-021-04188-4 |
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