Targeting Protein Kinase G to Treat Cardiac Proteotoxicity
Impaired or insufficient protein kinase G (PKG) signaling and protein quality control (PQC) are hallmarks of most forms of cardiac disease, including heart failure. Their dysregulation has been shown to contribute to and exacerbate cardiac hypertrophy and remodeling, reduced cell survival and diseas...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7399205/ https://www.ncbi.nlm.nih.gov/pubmed/32848832 http://dx.doi.org/10.3389/fphys.2020.00858 |
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author | Oeing, Christian U. Mishra, Sumita Dunkerly-Eyring, Brittany L. Ranek, Mark J. |
author_facet | Oeing, Christian U. Mishra, Sumita Dunkerly-Eyring, Brittany L. Ranek, Mark J. |
author_sort | Oeing, Christian U. |
collection | PubMed |
description | Impaired or insufficient protein kinase G (PKG) signaling and protein quality control (PQC) are hallmarks of most forms of cardiac disease, including heart failure. Their dysregulation has been shown to contribute to and exacerbate cardiac hypertrophy and remodeling, reduced cell survival and disease pathogenesis. Enhancement of PKG signaling and PQC are associated with improved cardiac function and survival in many pre-clinical models of heart disease. While many clinically used pharmacological approaches exist to stimulate PKG, there are no FDA-approved therapies to safely enhance cardiomyocyte PQC. The latter is predominantly due to our lack of knowledge and identification of proteins regulating cardiomyocyte PQC. Recently, multiple studies have demonstrated that PKG regulates PQC in the heart, both during physiological and pathological states. These studies tested already FDA-approved pharmacological therapies to activate PKG, which enhanced cardiomyocyte PQC and alleviated cardiac disease. This review examines the roles of PKG and PQC during disease pathogenesis and summarizes the experimental and clinical data supporting the utility of stimulating PKG to target cardiac proteotoxicity. |
format | Online Article Text |
id | pubmed-7399205 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-73992052020-08-25 Targeting Protein Kinase G to Treat Cardiac Proteotoxicity Oeing, Christian U. Mishra, Sumita Dunkerly-Eyring, Brittany L. Ranek, Mark J. Front Physiol Physiology Impaired or insufficient protein kinase G (PKG) signaling and protein quality control (PQC) are hallmarks of most forms of cardiac disease, including heart failure. Their dysregulation has been shown to contribute to and exacerbate cardiac hypertrophy and remodeling, reduced cell survival and disease pathogenesis. Enhancement of PKG signaling and PQC are associated with improved cardiac function and survival in many pre-clinical models of heart disease. While many clinically used pharmacological approaches exist to stimulate PKG, there are no FDA-approved therapies to safely enhance cardiomyocyte PQC. The latter is predominantly due to our lack of knowledge and identification of proteins regulating cardiomyocyte PQC. Recently, multiple studies have demonstrated that PKG regulates PQC in the heart, both during physiological and pathological states. These studies tested already FDA-approved pharmacological therapies to activate PKG, which enhanced cardiomyocyte PQC and alleviated cardiac disease. This review examines the roles of PKG and PQC during disease pathogenesis and summarizes the experimental and clinical data supporting the utility of stimulating PKG to target cardiac proteotoxicity. Frontiers Media S.A. 2020-07-28 /pmc/articles/PMC7399205/ /pubmed/32848832 http://dx.doi.org/10.3389/fphys.2020.00858 Text en Copyright © 2020 Oeing, Mishra, Dunkerly-Eyring and Ranek. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Physiology Oeing, Christian U. Mishra, Sumita Dunkerly-Eyring, Brittany L. Ranek, Mark J. Targeting Protein Kinase G to Treat Cardiac Proteotoxicity |
title | Targeting Protein Kinase G to Treat Cardiac Proteotoxicity |
title_full | Targeting Protein Kinase G to Treat Cardiac Proteotoxicity |
title_fullStr | Targeting Protein Kinase G to Treat Cardiac Proteotoxicity |
title_full_unstemmed | Targeting Protein Kinase G to Treat Cardiac Proteotoxicity |
title_short | Targeting Protein Kinase G to Treat Cardiac Proteotoxicity |
title_sort | targeting protein kinase g to treat cardiac proteotoxicity |
topic | Physiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7399205/ https://www.ncbi.nlm.nih.gov/pubmed/32848832 http://dx.doi.org/10.3389/fphys.2020.00858 |
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