RGD Reference Report - GCN5-mediated regulation of pathological cardiac hypertrophy via activation of the TAK1-JNK/p38 signaling pathway. - Rat Genome Database

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GCN5-mediated regulation of pathological cardiac hypertrophy via activation of the TAK1-JNK/p38 signaling pathway.

Authors: Li, Jia  Yan, Chenghui  Wang, Yilong  Chen, Can  Yu, Haibo  Liu, Dan  Huang, Kai  Han, Yaling 
Citation: Li J, etal., Cell Death Dis. 2022 Apr 30;13(4):421. doi: 10.1038/s41419-022-04881-y.
RGD ID: 155791668
Pubmed: PMID:35490166   (View Abstract at PubMed)
PMCID: PMC9056507   (View Article at PubMed Central)
DOI: DOI:10.1038/s41419-022-04881-y   (Journal Full-text)

Pathological cardiac hypertrophy is a process of abnormal remodeling of cardiomyocytes in response to pressure overload or other stress stimuli, resulting in myocardial injury, which is a major risk factor for heart failure, leading to increased morbidity and mortality. General control nonrepressed protein 5 (GCN5)/lysine acetyltransferase 2 A, a member of the histone acetyltransferase and lysine acetyltransferase families, regulates a variety of physiological and pathological events. However, the function of GCN5 in pathological cardiac hypertrophy remains unclear. This study aimed to explore the role of GCN5 in the development of pathological cardiac hypertrophy. GCN5 expression was increased in isolated neonatal rat cardiomyocytes (NRCMs) and mouse hearts of a hypertrophic mouse model. GCN5 overexpression aggravated the cardiac hypertrophy triggered by transverse aortic constriction surgery. In contrast, inhibition of GCN5 impairs the development of pathological cardiac hypertrophy. Similar results were obtained upon stimulation of NRCMs (having GCN5 overexpressed or knocked down) with phenylephrine. Mechanistically, our results indicate that GCN5 exacerbates cardiac hypertrophy via excessive activation of the transforming growth factor β-activated kinase 1 (TAK1)-c-Jun N-terminal kinase (JNK)/p38 signaling pathway. Using a TAK1-specific inhibitor in rescue experiments confirmed that the activation of TAK1 is essential for GCN5-mediated cardiac hypertrophy. In summary, the current study elucidated the role of GCN5 in promotion of cardiac hypertrophy, thereby implying it to be a potential target for treatment.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Cardiomegaly  ISOMap3k7 (Mus musculus)155791668; 155791668protein:increased phosphorylation:heart (mouse)RGD 
Cardiomegaly  IEP 155791668protein:increased phosphorylation:heart (mouse)RGD 

Gene-Chemical Interaction Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
phenylephrine increases phosphorylationISOMap3k7 (Rattus norvegicus)155791668; 155791668Phenylephrine increases phosphorylation of Map3k7 protein in neonatal cardiomyocytesRGD 
phenylephrine increases phosphorylationEXP 155791668Phenylephrine increases phosphorylation of Map3k7 protein in neonatal cardiomyocytesRGD 

Objects Annotated

Genes (Rattus norvegicus)
Map3k7  (mitogen activated protein kinase kinase kinase 7)

Genes (Mus musculus)
Map3k7  (mitogen-activated protein kinase kinase kinase 7)

Genes (Homo sapiens)
MAP3K7  (mitogen-activated protein kinase kinase kinase 7)


Additional Information