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SARS-CoV-2 Causes Lung Inflammation through Metabolic Reprogramming and RAGE
Clinical studies indicate that patients infected with SARS-CoV-2 develop hyperinflammation, which correlates with increased mortality. The SARS-CoV-2/COVID-19-dependent inflammation is thought to occur via increased cytokine production and hyperactivity of RAGE in several cell types, a phenomenon ob...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9143006/ https://www.ncbi.nlm.nih.gov/pubmed/35632725 http://dx.doi.org/10.3390/v14050983 |
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author | Allen, Charles N. S. Santerre, Maryline Arjona, Sterling P. Ghaleb, Lea J. Herzi, Muna Llewellyn, Megan D. Shcherbik, Natalia Sawaya, Bassel E. |
author_facet | Allen, Charles N. S. Santerre, Maryline Arjona, Sterling P. Ghaleb, Lea J. Herzi, Muna Llewellyn, Megan D. Shcherbik, Natalia Sawaya, Bassel E. |
author_sort | Allen, Charles N. S. |
collection | PubMed |
description | Clinical studies indicate that patients infected with SARS-CoV-2 develop hyperinflammation, which correlates with increased mortality. The SARS-CoV-2/COVID-19-dependent inflammation is thought to occur via increased cytokine production and hyperactivity of RAGE in several cell types, a phenomenon observed for other disorders and diseases. Metabolic reprogramming has been shown to contribute to inflammation and is considered a hallmark of cancer, neurodegenerative diseases, and viral infections. Malfunctioning glycolysis, which normally aims to convert glucose into pyruvate, leads to the accumulation of advanced glycation end products (AGEs). Being aberrantly generated, AGEs then bind to their receptor, RAGE, and activate several pro-inflammatory genes, such as IL-1b and IL-6, thus, increasing hypoxia and inducing senescence. Using the lung epithelial cell (BEAS-2B) line, we demonstrated that SARS-CoV-2 proteins reprogram the cellular metabolism and increase pyruvate kinase muscle isoform 2 (PKM2). This deregulation promotes the accumulation of AGEs and senescence induction. We showed the ability of the PKM2 stabilizer, Tepp-46, to reverse the observed glycolysis changes/alterations and restore this essential metabolic process. |
format | Online Article Text |
id | pubmed-9143006 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-91430062022-05-29 SARS-CoV-2 Causes Lung Inflammation through Metabolic Reprogramming and RAGE Allen, Charles N. S. Santerre, Maryline Arjona, Sterling P. Ghaleb, Lea J. Herzi, Muna Llewellyn, Megan D. Shcherbik, Natalia Sawaya, Bassel E. Viruses Article Clinical studies indicate that patients infected with SARS-CoV-2 develop hyperinflammation, which correlates with increased mortality. The SARS-CoV-2/COVID-19-dependent inflammation is thought to occur via increased cytokine production and hyperactivity of RAGE in several cell types, a phenomenon observed for other disorders and diseases. Metabolic reprogramming has been shown to contribute to inflammation and is considered a hallmark of cancer, neurodegenerative diseases, and viral infections. Malfunctioning glycolysis, which normally aims to convert glucose into pyruvate, leads to the accumulation of advanced glycation end products (AGEs). Being aberrantly generated, AGEs then bind to their receptor, RAGE, and activate several pro-inflammatory genes, such as IL-1b and IL-6, thus, increasing hypoxia and inducing senescence. Using the lung epithelial cell (BEAS-2B) line, we demonstrated that SARS-CoV-2 proteins reprogram the cellular metabolism and increase pyruvate kinase muscle isoform 2 (PKM2). This deregulation promotes the accumulation of AGEs and senescence induction. We showed the ability of the PKM2 stabilizer, Tepp-46, to reverse the observed glycolysis changes/alterations and restore this essential metabolic process. MDPI 2022-05-06 /pmc/articles/PMC9143006/ /pubmed/35632725 http://dx.doi.org/10.3390/v14050983 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Allen, Charles N. S. Santerre, Maryline Arjona, Sterling P. Ghaleb, Lea J. Herzi, Muna Llewellyn, Megan D. Shcherbik, Natalia Sawaya, Bassel E. SARS-CoV-2 Causes Lung Inflammation through Metabolic Reprogramming and RAGE |
title | SARS-CoV-2 Causes Lung Inflammation through Metabolic Reprogramming and RAGE |
title_full | SARS-CoV-2 Causes Lung Inflammation through Metabolic Reprogramming and RAGE |
title_fullStr | SARS-CoV-2 Causes Lung Inflammation through Metabolic Reprogramming and RAGE |
title_full_unstemmed | SARS-CoV-2 Causes Lung Inflammation through Metabolic Reprogramming and RAGE |
title_short | SARS-CoV-2 Causes Lung Inflammation through Metabolic Reprogramming and RAGE |
title_sort | sars-cov-2 causes lung inflammation through metabolic reprogramming and rage |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9143006/ https://www.ncbi.nlm.nih.gov/pubmed/35632725 http://dx.doi.org/10.3390/v14050983 |
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