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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...

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Autores principales: Chen, Lijuan, Huang, Jia, Ji, Yanxiao, Zhang, Xiaojing, Wang, Pixiao, Deng, Keqiong, Jiang, Xi, Ma, Genshan, Li, Hongliang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2016
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.
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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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