Cardiac-specific deletion of GCN5L1 restricts recovery from ischemia-reperfusion injury.
J Mol Cell Cardiol
; 129: 69-78, 2019 04.
Article
em En
| MEDLINE
| ID: mdl-30776374
ABSTRACT
GCN5L1 regulates mitochondrial protein acetylation, cellular bioenergetics, reactive oxygen species (ROS) generation, and organelle positioning in a number of diverse cell types. However, the functional role of GCN5L1 in the heart is currently unknown. As many of the factors regulated by GCN5L1 play a major role in ischemia-reperfusion (I/R) injury, we sought to determine if GCN5L1 is an important nexus in the response to cardiac ischemic stress. Deletion of GCN5L1 in cardiomyocytes resulted in impaired myocardial post-ischemic function and increased infarct development in isolated work-performing hearts. GCN5L1 knockout hearts displayed hallmarks of ROS damage, and scavenging of ROS restored cardiac function and reduced infarct volume in vivo. GCN5L1 knockdown in cardiac-derived AC16 cells was associated with reduced activation of the pro-survival MAP kinase ERK1/2, which was also reversed by ROS scavenging, leading to restored cell viability. We therefore conclude that GCN5L1 activity provides an important protection against I/R induced, ROS-mediated damage in the ischemic heart.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Especificidade de Órgãos
/
Traumatismo por Reperfusão Miocárdica
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Deleção de Genes
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Recuperação de Função Fisiológica
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Proteínas Mitocondriais
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Miocárdio
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Proteínas do Tecido Nervoso
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
J Mol Cell Cardiol
Ano de publicação:
2019
Tipo de documento:
Article