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Local IGF-1 isoform protects cardiomyocytes from hypertrophic and oxidative stresses via SirT1 activity
Oxidative and hypertrophic stresses contribute to the pathogenesis of heart failure. Insulin-like growth factor-1 (IGF-1) is a peptide hormone with a complex post-transcriptional regulation, generating distinct isoforms. Locally acting IGF-1 isoform (mIGF-1) helps the heart to recover from toxic inj...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2837204/ https://www.ncbi.nlm.nih.gov/pubmed/20228935 |
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author | Vinciguerra, Manlio Santini, Maria Paola Claycomb, William C. Ladurner, Andreas G. Rosenthal, Nadia |
author_facet | Vinciguerra, Manlio Santini, Maria Paola Claycomb, William C. Ladurner, Andreas G. Rosenthal, Nadia |
author_sort | Vinciguerra, Manlio |
collection | PubMed |
description | Oxidative and hypertrophic stresses contribute to the pathogenesis of heart failure. Insulin-like growth factor-1 (IGF-1) is a peptide hormone with a complex post-transcriptional regulation, generating distinct isoforms. Locally acting IGF-1 isoform (mIGF-1) helps the heart to recover from toxic injury and from infarct. In the murine heart, moderate overexpression of the NAD(+)-dependent deacetylase SirT1 was reported to mitigate oxidative stress. SirT1 is known to promote lifespan extension and to protect from metabolic challenges. Circulating IGF-1 and SirT1 play antagonizing biological roles and share molecular targets in the heart, in turn affecting cardiomyocyte physiology. However, how different IGF-1 isoforms may impact SirT1 and affect cardiomyocyte function is unknown. Here we show that locally acting mIGF-1 increases SirT1 expression/activity, whereas circulating IGF-1 isoform does not affect it, in cultured HL-1 and neonatal cardiomyocytes. mIGF-1-induced SirT1 activity exerts protection against angiotensin II (Ang II)-triggered hypertrophy and against paraquat (PQ) and Ang II-induced oxidative stress. Conversely, circulating IGF-1 triggered itself oxidative stress and cardiomyocyte hypertrophy. Interestingly, potent cardio-protective genes (adiponectin, UCP-1 and MT-2) were increased specifically in mIGF-1-overexpressing cardiomyocytes, in a SirT1-dependent fashion. Thus, mIGF-1 protects cardiomyocytes from oxidative and hypertrophic stresses via SirT1 activity, and may represent a promising cardiac therapeutic. |
format | Text |
id | pubmed-2837204 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-28372042010-03-12 Local IGF-1 isoform protects cardiomyocytes from hypertrophic and oxidative stresses via SirT1 activity Vinciguerra, Manlio Santini, Maria Paola Claycomb, William C. Ladurner, Andreas G. Rosenthal, Nadia Aging (Albany NY) Research Article Oxidative and hypertrophic stresses contribute to the pathogenesis of heart failure. Insulin-like growth factor-1 (IGF-1) is a peptide hormone with a complex post-transcriptional regulation, generating distinct isoforms. Locally acting IGF-1 isoform (mIGF-1) helps the heart to recover from toxic injury and from infarct. In the murine heart, moderate overexpression of the NAD(+)-dependent deacetylase SirT1 was reported to mitigate oxidative stress. SirT1 is known to promote lifespan extension and to protect from metabolic challenges. Circulating IGF-1 and SirT1 play antagonizing biological roles and share molecular targets in the heart, in turn affecting cardiomyocyte physiology. However, how different IGF-1 isoforms may impact SirT1 and affect cardiomyocyte function is unknown. Here we show that locally acting mIGF-1 increases SirT1 expression/activity, whereas circulating IGF-1 isoform does not affect it, in cultured HL-1 and neonatal cardiomyocytes. mIGF-1-induced SirT1 activity exerts protection against angiotensin II (Ang II)-triggered hypertrophy and against paraquat (PQ) and Ang II-induced oxidative stress. Conversely, circulating IGF-1 triggered itself oxidative stress and cardiomyocyte hypertrophy. Interestingly, potent cardio-protective genes (adiponectin, UCP-1 and MT-2) were increased specifically in mIGF-1-overexpressing cardiomyocytes, in a SirT1-dependent fashion. Thus, mIGF-1 protects cardiomyocytes from oxidative and hypertrophic stresses via SirT1 activity, and may represent a promising cardiac therapeutic. Impact Journals LLC 2009-12-10 /pmc/articles/PMC2837204/ /pubmed/20228935 Text en Copyright: ©2010 Vinciguerra et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Vinciguerra, Manlio Santini, Maria Paola Claycomb, William C. Ladurner, Andreas G. Rosenthal, Nadia Local IGF-1 isoform protects cardiomyocytes from hypertrophic and oxidative stresses via SirT1 activity |
title | Local IGF-1 isoform protects cardiomyocytes from hypertrophic and
oxidative stresses via SirT1 activity |
title_full | Local IGF-1 isoform protects cardiomyocytes from hypertrophic and
oxidative stresses via SirT1 activity |
title_fullStr | Local IGF-1 isoform protects cardiomyocytes from hypertrophic and
oxidative stresses via SirT1 activity |
title_full_unstemmed | Local IGF-1 isoform protects cardiomyocytes from hypertrophic and
oxidative stresses via SirT1 activity |
title_short | Local IGF-1 isoform protects cardiomyocytes from hypertrophic and
oxidative stresses via SirT1 activity |
title_sort | local igf-1 isoform protects cardiomyocytes from hypertrophic and
oxidative stresses via sirt1 activity |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2837204/ https://www.ncbi.nlm.nih.gov/pubmed/20228935 |
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