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...

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Autores principales: Oeing, Christian U., Mishra, Sumita, Dunkerly-Eyring, Brittany L., Ranek, Mark J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
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.
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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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