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An ACE2/Mas-related receptor MrgE axis in dopaminergic neuron mitochondria
ACE2 plays a pivotal role in the balance between the pro-oxidative pro-inflammatory and the anti-oxidative anti-inflammatory arms of the renin-angiotensin system. Furthermore, ACE2 is the entry receptor for SARS-CoV-2. Clarification of ACE2-related mechanisms is crucial for the understanding of COVI...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8346680/ https://www.ncbi.nlm.nih.gov/pubmed/34333284 http://dx.doi.org/10.1016/j.redox.2021.102078 |
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author | Valenzuela, Rita Rodriguez-Perez, Ana I. Costa-Besada, Maria A. Rivas-Santisteban, Rafael Garrido-Gil, Pablo Lopez-Lopez, Andrea Navarro, Gemma Lanciego, Jose L. Franco, Rafael Labandeira-Garcia, Jose L. |
author_facet | Valenzuela, Rita Rodriguez-Perez, Ana I. Costa-Besada, Maria A. Rivas-Santisteban, Rafael Garrido-Gil, Pablo Lopez-Lopez, Andrea Navarro, Gemma Lanciego, Jose L. Franco, Rafael Labandeira-Garcia, Jose L. |
author_sort | Valenzuela, Rita |
collection | PubMed |
description | ACE2 plays a pivotal role in the balance between the pro-oxidative pro-inflammatory and the anti-oxidative anti-inflammatory arms of the renin-angiotensin system. Furthermore, ACE2 is the entry receptor for SARS-CoV-2. Clarification of ACE2-related mechanisms is crucial for the understanding of COVID-19 and other oxidative stress and inflammation-related processes. In rat and monkey brain, we discovered that the intracellular ACE2 and its products Ang 1–7 and alamandine are highly concentrated in the mitochondria and bind to a new mitochondrial Mas-related receptor MrgE (MrgE) to produce nitric oxide. We found MrgE expressed in neurons and glia of rodents and primates in the substantia nigra and different brain regions. In the mitochondria, ACE2 and MrgE expressions decreased and NOX4 increased with aging. This new ACE2/MrgE/NO axis may play a major role in mitochondrial regulation of oxidative stress in neurons, and possibly other cells. Therefore, dysregulation of the mitochondrial ACE2/MrgE/NO axis may play a major role in neurodegenerative processes of dopaminergic neurons, where mitochondrial dysfunction and oxidative stress play a crucial role. Since ACE2 binds SARS-CoV-2 spike protein, the mitochondrial ACE2/MrgE/NO axis may also play a role in SARS-CoV-2 cellular effects. |
format | Online Article Text |
id | pubmed-8346680 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-83466802021-08-11 An ACE2/Mas-related receptor MrgE axis in dopaminergic neuron mitochondria Valenzuela, Rita Rodriguez-Perez, Ana I. Costa-Besada, Maria A. Rivas-Santisteban, Rafael Garrido-Gil, Pablo Lopez-Lopez, Andrea Navarro, Gemma Lanciego, Jose L. Franco, Rafael Labandeira-Garcia, Jose L. Redox Biol Research Paper ACE2 plays a pivotal role in the balance between the pro-oxidative pro-inflammatory and the anti-oxidative anti-inflammatory arms of the renin-angiotensin system. Furthermore, ACE2 is the entry receptor for SARS-CoV-2. Clarification of ACE2-related mechanisms is crucial for the understanding of COVID-19 and other oxidative stress and inflammation-related processes. In rat and monkey brain, we discovered that the intracellular ACE2 and its products Ang 1–7 and alamandine are highly concentrated in the mitochondria and bind to a new mitochondrial Mas-related receptor MrgE (MrgE) to produce nitric oxide. We found MrgE expressed in neurons and glia of rodents and primates in the substantia nigra and different brain regions. In the mitochondria, ACE2 and MrgE expressions decreased and NOX4 increased with aging. This new ACE2/MrgE/NO axis may play a major role in mitochondrial regulation of oxidative stress in neurons, and possibly other cells. Therefore, dysregulation of the mitochondrial ACE2/MrgE/NO axis may play a major role in neurodegenerative processes of dopaminergic neurons, where mitochondrial dysfunction and oxidative stress play a crucial role. Since ACE2 binds SARS-CoV-2 spike protein, the mitochondrial ACE2/MrgE/NO axis may also play a role in SARS-CoV-2 cellular effects. Elsevier 2021-07-22 /pmc/articles/PMC8346680/ /pubmed/34333284 http://dx.doi.org/10.1016/j.redox.2021.102078 Text en © 2021 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Paper Valenzuela, Rita Rodriguez-Perez, Ana I. Costa-Besada, Maria A. Rivas-Santisteban, Rafael Garrido-Gil, Pablo Lopez-Lopez, Andrea Navarro, Gemma Lanciego, Jose L. Franco, Rafael Labandeira-Garcia, Jose L. An ACE2/Mas-related receptor MrgE axis in dopaminergic neuron mitochondria |
title | An ACE2/Mas-related receptor MrgE axis in dopaminergic neuron mitochondria |
title_full | An ACE2/Mas-related receptor MrgE axis in dopaminergic neuron mitochondria |
title_fullStr | An ACE2/Mas-related receptor MrgE axis in dopaminergic neuron mitochondria |
title_full_unstemmed | An ACE2/Mas-related receptor MrgE axis in dopaminergic neuron mitochondria |
title_short | An ACE2/Mas-related receptor MrgE axis in dopaminergic neuron mitochondria |
title_sort | ace2/mas-related receptor mrge axis in dopaminergic neuron mitochondria |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8346680/ https://www.ncbi.nlm.nih.gov/pubmed/34333284 http://dx.doi.org/10.1016/j.redox.2021.102078 |
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