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Induction of Cardiac Pathology: Endogenous versus Exogenous Nrf2 Upregulation

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a master regulator of the endogenous antioxidant response to reactive oxygen species as well as a controller of Phase II detoxification in response to xenobiotics. This amenity to specific external manipulation exploits the binding affinity of Nr...

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Detalles Bibliográficos
Autores principales: Mathis, Bryan J., Kato, Hideyuki, Hiramatsu, Yuji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9736027/
https://www.ncbi.nlm.nih.gov/pubmed/36497112
http://dx.doi.org/10.3390/cells11233855
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author Mathis, Bryan J.
Kato, Hideyuki
Hiramatsu, Yuji
author_facet Mathis, Bryan J.
Kato, Hideyuki
Hiramatsu, Yuji
author_sort Mathis, Bryan J.
collection PubMed
description Nuclear factor erythroid 2-related factor 2 (Nrf2) is a master regulator of the endogenous antioxidant response to reactive oxygen species as well as a controller of Phase II detoxification in response to xenobiotics. This amenity to specific external manipulation exploits the binding affinity of Nrf2 for its constitutive repressor and degradation facilitator Kelch-like erythroid cell-derived protein with CNC homology-associated protein 1 (Keap1). Derived from both natural and synthesized origins, these compounds have been extensively tested without definitive beneficial results. Unfortunately, multiple terminated trials have shown a negative side to Nrf2 with regard to cardiac pathologies while animal-based studies have demonstrated cardiomyocyte hypertrophy and heart failure after chronic Nrf2 upregulation. Putatively based on autophagic control of Nrf2 activity-modulating upstream factors, new evidence of miRNA involvement has added complexity to this mechanism. What follows is an extensive survey of Nrf2-regulating exogenous compounds that may promote cardiomyopathy, clinical trial evidence, and a comparison to exercise-induced factors that also upregulate Nrf2 while preventing cardiac pathologies.
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spelling pubmed-97360272022-12-11 Induction of Cardiac Pathology: Endogenous versus Exogenous Nrf2 Upregulation Mathis, Bryan J. Kato, Hideyuki Hiramatsu, Yuji Cells Review Nuclear factor erythroid 2-related factor 2 (Nrf2) is a master regulator of the endogenous antioxidant response to reactive oxygen species as well as a controller of Phase II detoxification in response to xenobiotics. This amenity to specific external manipulation exploits the binding affinity of Nrf2 for its constitutive repressor and degradation facilitator Kelch-like erythroid cell-derived protein with CNC homology-associated protein 1 (Keap1). Derived from both natural and synthesized origins, these compounds have been extensively tested without definitive beneficial results. Unfortunately, multiple terminated trials have shown a negative side to Nrf2 with regard to cardiac pathologies while animal-based studies have demonstrated cardiomyocyte hypertrophy and heart failure after chronic Nrf2 upregulation. Putatively based on autophagic control of Nrf2 activity-modulating upstream factors, new evidence of miRNA involvement has added complexity to this mechanism. What follows is an extensive survey of Nrf2-regulating exogenous compounds that may promote cardiomyopathy, clinical trial evidence, and a comparison to exercise-induced factors that also upregulate Nrf2 while preventing cardiac pathologies. MDPI 2022-11-30 /pmc/articles/PMC9736027/ /pubmed/36497112 http://dx.doi.org/10.3390/cells11233855 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 Review
Mathis, Bryan J.
Kato, Hideyuki
Hiramatsu, Yuji
Induction of Cardiac Pathology: Endogenous versus Exogenous Nrf2 Upregulation
title Induction of Cardiac Pathology: Endogenous versus Exogenous Nrf2 Upregulation
title_full Induction of Cardiac Pathology: Endogenous versus Exogenous Nrf2 Upregulation
title_fullStr Induction of Cardiac Pathology: Endogenous versus Exogenous Nrf2 Upregulation
title_full_unstemmed Induction of Cardiac Pathology: Endogenous versus Exogenous Nrf2 Upregulation
title_short Induction of Cardiac Pathology: Endogenous versus Exogenous Nrf2 Upregulation
title_sort induction of cardiac pathology: endogenous versus exogenous nrf2 upregulation
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9736027/
https://www.ncbi.nlm.nih.gov/pubmed/36497112
http://dx.doi.org/10.3390/cells11233855
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