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Synthetic Growth Hormone-Releasing Peptides (GHRPs): A Historical Appraisal of the Evidences Supporting Their Cytoprotective Effects

BACKGROUND: Growth hormone-releasing peptides (GHRPs) constitute a group of small synthetic peptides that stimulate the growth hormone secretion and the downstream axis activity. Mounting evidences since the early 1980s delineated unexpected pharmacological cardioprotective and cytoprotective proper...

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Autores principales: Berlanga-Acosta, Jorge, Abreu-Cruz, Angel, Barco Herrera, Diana García-del, Mendoza-Marí, Yssel, Rodríguez-Ulloa, Arielis, García-Ojalvo, Ariana, Falcón-Cama, Viviana, Hernández-Bernal, Francisco, Beichen, Qu, Guillén-Nieto, Gerardo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5392015/
https://www.ncbi.nlm.nih.gov/pubmed/28469491
http://dx.doi.org/10.1177/1179546817694558
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author Berlanga-Acosta, Jorge
Abreu-Cruz, Angel
Barco Herrera, Diana García-del
Mendoza-Marí, Yssel
Rodríguez-Ulloa, Arielis
García-Ojalvo, Ariana
Falcón-Cama, Viviana
Hernández-Bernal, Francisco
Beichen, Qu
Guillén-Nieto, Gerardo
author_facet Berlanga-Acosta, Jorge
Abreu-Cruz, Angel
Barco Herrera, Diana García-del
Mendoza-Marí, Yssel
Rodríguez-Ulloa, Arielis
García-Ojalvo, Ariana
Falcón-Cama, Viviana
Hernández-Bernal, Francisco
Beichen, Qu
Guillén-Nieto, Gerardo
author_sort Berlanga-Acosta, Jorge
collection PubMed
description BACKGROUND: Growth hormone-releasing peptides (GHRPs) constitute a group of small synthetic peptides that stimulate the growth hormone secretion and the downstream axis activity. Mounting evidences since the early 1980s delineated unexpected pharmacological cardioprotective and cytoprotective properties for the GHRPs. However, despite intense basic pharmacological research, alternatives to prevent cell and tissue demise before lethal insults have remained as an empty niche in the clinical armamentarium. Here, we have rigorously reviewed the investigational development of GHRPs and their clinical niching perspectives. METHODOLOGY: PubMed/MEDLINE databases, including original research and review articles, were explored. The search design was date escalated from 1980 and included articles in English only. RESULTS AND CONCLUSIONS: GHRPs bind to two different receptors (GHS-R1a and CD36), which redundantly or independently exert relevant biological effects. GHRPs’ binding to CD36 activates prosurvival pathways such as PI-3K/AKT1, thus reducing cellular death. Furthermore, GHRPs decrease reactive oxygen species (ROS) spillover, enhance the antioxidant defenses, and reduce inflammation. These cytoprotective abilities have been revealed in cardiac, neuronal, gastrointestinal, and hepatic cells, representing a comprehensive spectrum of protection of parenchymal organs. Antifibrotic effects have been attributed to some of the GHRPs by counteracting fibrogenic cytokines. In addition, GHRP family members have shown a potent myotropic effect by promoting anabolia and inhibiting catabolia. Finally, GHRPs exhibit a broad safety profile in preclinical and clinical settings. Despite these fragmented lines incite to envision multiple pharmacological uses for GHRPs, especially as a myocardial reperfusion damage-attenuating candidate, this family of “drugable” peptides awaits for a definitive clinical niche.
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spelling pubmed-53920152017-05-03 Synthetic Growth Hormone-Releasing Peptides (GHRPs): A Historical Appraisal of the Evidences Supporting Their Cytoprotective Effects Berlanga-Acosta, Jorge Abreu-Cruz, Angel Barco Herrera, Diana García-del Mendoza-Marí, Yssel Rodríguez-Ulloa, Arielis García-Ojalvo, Ariana Falcón-Cama, Viviana Hernández-Bernal, Francisco Beichen, Qu Guillén-Nieto, Gerardo Clin Med Insights Cardiol Review BACKGROUND: Growth hormone-releasing peptides (GHRPs) constitute a group of small synthetic peptides that stimulate the growth hormone secretion and the downstream axis activity. Mounting evidences since the early 1980s delineated unexpected pharmacological cardioprotective and cytoprotective properties for the GHRPs. However, despite intense basic pharmacological research, alternatives to prevent cell and tissue demise before lethal insults have remained as an empty niche in the clinical armamentarium. Here, we have rigorously reviewed the investigational development of GHRPs and their clinical niching perspectives. METHODOLOGY: PubMed/MEDLINE databases, including original research and review articles, were explored. The search design was date escalated from 1980 and included articles in English only. RESULTS AND CONCLUSIONS: GHRPs bind to two different receptors (GHS-R1a and CD36), which redundantly or independently exert relevant biological effects. GHRPs’ binding to CD36 activates prosurvival pathways such as PI-3K/AKT1, thus reducing cellular death. Furthermore, GHRPs decrease reactive oxygen species (ROS) spillover, enhance the antioxidant defenses, and reduce inflammation. These cytoprotective abilities have been revealed in cardiac, neuronal, gastrointestinal, and hepatic cells, representing a comprehensive spectrum of protection of parenchymal organs. Antifibrotic effects have been attributed to some of the GHRPs by counteracting fibrogenic cytokines. In addition, GHRP family members have shown a potent myotropic effect by promoting anabolia and inhibiting catabolia. Finally, GHRPs exhibit a broad safety profile in preclinical and clinical settings. Despite these fragmented lines incite to envision multiple pharmacological uses for GHRPs, especially as a myocardial reperfusion damage-attenuating candidate, this family of “drugable” peptides awaits for a definitive clinical niche. SAGE Publications 2017-03-02 /pmc/articles/PMC5392015/ /pubmed/28469491 http://dx.doi.org/10.1177/1179546817694558 Text en © The Author(s) 2017 http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Review
Berlanga-Acosta, Jorge
Abreu-Cruz, Angel
Barco Herrera, Diana García-del
Mendoza-Marí, Yssel
Rodríguez-Ulloa, Arielis
García-Ojalvo, Ariana
Falcón-Cama, Viviana
Hernández-Bernal, Francisco
Beichen, Qu
Guillén-Nieto, Gerardo
Synthetic Growth Hormone-Releasing Peptides (GHRPs): A Historical Appraisal of the Evidences Supporting Their Cytoprotective Effects
title Synthetic Growth Hormone-Releasing Peptides (GHRPs): A Historical Appraisal of the Evidences Supporting Their Cytoprotective Effects
title_full Synthetic Growth Hormone-Releasing Peptides (GHRPs): A Historical Appraisal of the Evidences Supporting Their Cytoprotective Effects
title_fullStr Synthetic Growth Hormone-Releasing Peptides (GHRPs): A Historical Appraisal of the Evidences Supporting Their Cytoprotective Effects
title_full_unstemmed Synthetic Growth Hormone-Releasing Peptides (GHRPs): A Historical Appraisal of the Evidences Supporting Their Cytoprotective Effects
title_short Synthetic Growth Hormone-Releasing Peptides (GHRPs): A Historical Appraisal of the Evidences Supporting Their Cytoprotective Effects
title_sort synthetic growth hormone-releasing peptides (ghrps): a historical appraisal of the evidences supporting their cytoprotective effects
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5392015/
https://www.ncbi.nlm.nih.gov/pubmed/28469491
http://dx.doi.org/10.1177/1179546817694558
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