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Tripartite motif 32 prevents pathological cardiac hypertrophy
TRIM32 (tripartite motif 32) is widely accepted to be an E3 ligase that interacts with and eventually ubiquitylates multiple substrates. TRIM32 mutants have been associated with LGMD-2H (limb girdle muscular dystrophy 2H). However, whether TRIM32 is involved in cardiac hypertrophy induced by biomech...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Portland Press Ltd.
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4847158/ https://www.ncbi.nlm.nih.gov/pubmed/26884348 http://dx.doi.org/10.1042/CS20150619 |
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author | Chen, Lijuan Huang, Jia Ji, Yanxiao Zhang, Xiaojing Wang, Pixiao Deng, Keqiong Jiang, Xi Ma, Genshan Li, Hongliang |
author_facet | Chen, Lijuan Huang, Jia Ji, Yanxiao Zhang, Xiaojing Wang, Pixiao Deng, Keqiong Jiang, Xi Ma, Genshan Li, Hongliang |
author_sort | Chen, Lijuan |
collection | PubMed |
description | TRIM32 (tripartite motif 32) is widely accepted to be an E3 ligase that interacts with and eventually ubiquitylates multiple substrates. TRIM32 mutants have been associated with LGMD-2H (limb girdle muscular dystrophy 2H). However, whether TRIM32 is involved in cardiac hypertrophy induced by biomechanical stresses and neurohumoral mediators remains unclear. We generated mice and isolated NRCMs (neonatal rat cardiomyocytes) that overexpressed or were deficient in TRIM32 to investigate the effect of TRIM32 on AB (aortic banding) or AngII (angiotensin II)-mediated cardiac hypertrophy. Echocardiography and both pathological and molecular analyses were used to determine the extent of cardiac hypertrophy and subsequent fibrosis. Our results showed that overexpression of TRIM32 in the heart significantly alleviated the hypertrophic response induced by pressure overload, whereas TRIM32 deficiency dramatically aggravated pathological cardiac remodelling. Similar results were also found in cultured NRCMs incubated with AngII. Mechanistically, the present study suggests that TRIM32 exerts cardioprotective action by interruption of Akt- but not MAPK (mitogen-dependent protein kinase)-dependent signalling pathways. Additionally, inactivation of Akt by LY294002 offset the exacerbated hypertrophic response induced by AB in TRIM32-deficient mice. In conclusion, the present study indicates that TRIM32 plays a protective role in AB-induced pathological cardiac remodelling by blocking Akt-dependent signalling. Therefore TRIM32 could be a novel therapeutic target for the prevention of cardiac hypertrophy and heart failure. |
format | Online Article Text |
id | pubmed-4847158 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Portland Press Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-48471582016-05-09 Tripartite motif 32 prevents pathological cardiac hypertrophy Chen, Lijuan Huang, Jia Ji, Yanxiao Zhang, Xiaojing Wang, Pixiao Deng, Keqiong Jiang, Xi Ma, Genshan Li, Hongliang Clin Sci (Lond) Original Papers TRIM32 (tripartite motif 32) is widely accepted to be an E3 ligase that interacts with and eventually ubiquitylates multiple substrates. TRIM32 mutants have been associated with LGMD-2H (limb girdle muscular dystrophy 2H). However, whether TRIM32 is involved in cardiac hypertrophy induced by biomechanical stresses and neurohumoral mediators remains unclear. We generated mice and isolated NRCMs (neonatal rat cardiomyocytes) that overexpressed or were deficient in TRIM32 to investigate the effect of TRIM32 on AB (aortic banding) or AngII (angiotensin II)-mediated cardiac hypertrophy. Echocardiography and both pathological and molecular analyses were used to determine the extent of cardiac hypertrophy and subsequent fibrosis. Our results showed that overexpression of TRIM32 in the heart significantly alleviated the hypertrophic response induced by pressure overload, whereas TRIM32 deficiency dramatically aggravated pathological cardiac remodelling. Similar results were also found in cultured NRCMs incubated with AngII. Mechanistically, the present study suggests that TRIM32 exerts cardioprotective action by interruption of Akt- but not MAPK (mitogen-dependent protein kinase)-dependent signalling pathways. Additionally, inactivation of Akt by LY294002 offset the exacerbated hypertrophic response induced by AB in TRIM32-deficient mice. In conclusion, the present study indicates that TRIM32 plays a protective role in AB-induced pathological cardiac remodelling by blocking Akt-dependent signalling. Therefore TRIM32 could be a novel therapeutic target for the prevention of cardiac hypertrophy and heart failure. Portland Press Ltd. 2016-04-01 2016-05-01 /pmc/articles/PMC4847158/ /pubmed/26884348 http://dx.doi.org/10.1042/CS20150619 Text en © 2016 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Papers Chen, Lijuan Huang, Jia Ji, Yanxiao Zhang, Xiaojing Wang, Pixiao Deng, Keqiong Jiang, Xi Ma, Genshan Li, Hongliang Tripartite motif 32 prevents pathological cardiac hypertrophy |
title | Tripartite motif 32 prevents pathological cardiac hypertrophy |
title_full | Tripartite motif 32 prevents pathological cardiac hypertrophy |
title_fullStr | Tripartite motif 32 prevents pathological cardiac hypertrophy |
title_full_unstemmed | Tripartite motif 32 prevents pathological cardiac hypertrophy |
title_short | Tripartite motif 32 prevents pathological cardiac hypertrophy |
title_sort | tripartite motif 32 prevents pathological cardiac hypertrophy |
topic | Original Papers |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4847158/ https://www.ncbi.nlm.nih.gov/pubmed/26884348 http://dx.doi.org/10.1042/CS20150619 |
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