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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| Format: | Article |
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MDPI AG
2022-11-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/23/3855 |
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| author | Bryan J. Mathis Hideyuki Kato Yuji Hiramatsu |
| author_facet | Bryan J. Mathis Hideyuki Kato Yuji Hiramatsu |
| author_sort | Bryan J. Mathis |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-09T17:51:02Z |
| format | Article |
| id | doaj.art-12b7e540818644468d2093f11076cc21 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T17:51:02Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-12b7e540818644468d2093f11076cc212023-11-24T10:44:56ZengMDPI AGCells2073-44092022-11-011123385510.3390/cells11233855Induction of Cardiac Pathology: Endogenous versus Exogenous Nrf2 UpregulationBryan J. Mathis0Hideyuki Kato1Yuji Hiramatsu2International Medical Center, University of Tsukuba Hospital, Tsukuba 305-8576, Ibaraki, JapanDepartment of Cardiovascular Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Ibaraki, JapanInternational Medical Center, University of Tsukuba Hospital, Tsukuba 305-8576, Ibaraki, JapanNuclear 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.https://www.mdpi.com/2073-4409/11/23/3855Nrf2Keap1cardiomyopathybardoloxoneReataCDDO |
| spellingShingle | Bryan J. Mathis Hideyuki Kato Yuji Hiramatsu Induction of Cardiac Pathology: Endogenous versus Exogenous Nrf2 Upregulation Cells Nrf2 Keap1 cardiomyopathy bardoloxone Reata CDDO |
| 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 | Nrf2 Keap1 cardiomyopathy bardoloxone Reata CDDO |
| url | https://www.mdpi.com/2073-4409/11/23/3855 |
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