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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.
  • Valenzuela R; Cellular and Molecular Neurobiology of Parkinson's Disease, Research Center for Molecular Medicine and Chronic Diseases (CIMUS), IDIS, University of Santiago de Compostela, Santiago de Compostela; Spain; Networking Research Center on Neurodegenerative Diseases (CIBERNED), Spain. Electronic address:
  • Rodriguez-Perez AI; Cellular and Molecular Neurobiology of Parkinson's Disease, Research Center for Molecular Medicine and Chronic Diseases (CIMUS), IDIS, University of Santiago de Compostela, Santiago de Compostela; Spain; Networking Research Center on Neurodegenerative Diseases (CIBERNED), Spain.
  • Costa-Besada MA; Cellular and Molecular Neurobiology of Parkinson's Disease, Research Center for Molecular Medicine and Chronic Diseases (CIMUS), IDIS, University of Santiago de Compostela, Santiago de Compostela; Spain; Cell and Developmental Biology Department, University College London, London, UK.
  • Rivas-Santisteban R; Networking Research Center on Neurodegenerative Diseases (CIBERNED), Spain; Laboratory of Molecular Neurobiology, Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona, Barcelona, Spain.
  • Garrido-Gil P; Cellular and Molecular Neurobiology of Parkinson's Disease, Research Center for Molecular Medicine and Chronic Diseases (CIMUS), IDIS, University of Santiago de Compostela, Santiago de Compostela; Spain; Networking Research Center on Neurodegenerative Diseases (CIBERNED), Spain.
  • Lopez-Lopez A; Cellular and Molecular Neurobiology of Parkinson's Disease, Research Center for Molecular Medicine and Chronic Diseases (CIMUS), IDIS, University of Santiago de Compostela, Santiago de Compostela; Spain.
  • Navarro G; Networking Research Center on Neurodegenerative Diseases (CIBERNED), Spain; Department of Biochemistry and Physiology, Faculty of Pharmacy, University of Barcelona, Barcelona, Spain.
  • Lanciego JL; Networking Research Center on Neurodegenerative Diseases (CIBERNED), Spain; Neuroscience Department, Center for Applied Medical Research (CIMA, IdiSNA), University of Navarra, Pamplona, Spain.
  • Franco R; Networking Research Center on Neurodegenerative Diseases (CIBERNED), Spain; Laboratory of Molecular Neurobiology, Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona, Barcelona, Spain.
  • Labandeira-Garcia JL; Cellular and Molecular Neurobiology of Parkinson's Disease, Research Center for Molecular Medicine and Chronic Diseases (CIMUS), IDIS, University of Santiago de Compostela, Santiago de Compostela; Spain; Networking Research Center on Neurodegenerative Diseases (CIBERNED), Spain. Electronic address:
Redox Biol ; 46: 102078, 2021 10.
Article in English | MEDLINE | ID: covidwho-1322332
ABSTRACT
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Receptors, G-Protein-Coupled / Dopaminergic Neurons / Angiotensin-Converting Enzyme 2 / Mitochondria Limits: Animals / Humans Language: English Journal: Redox Biol Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Receptors, G-Protein-Coupled / Dopaminergic Neurons / Angiotensin-Converting Enzyme 2 / Mitochondria Limits: Animals / Humans Language: English Journal: Redox Biol Year: 2021 Document Type: Article