MG-132 attenuates cardiac deterioration of viral myocarditis via AMPK pathway.
Biomed Pharmacother
; 126: 110091, 2020 Jun.
Article
em En
| MEDLINE
| ID: mdl-32278272
ABSTRACT
BACKGROUND:
Coxsackievirus B3 (CVB3) is the primary cause of infectious myocarditis. Aggressive immunological activation and apoptosis of myocytes contributes to progressive dysfunction of cardiac contraction and poor prognosis. MG-132, a proteasome inhibitor, regulates mitochondrial-mediated intrinsic myocardial apoptosis and downregulates NF-κB-mediated inflammation. Here, we determined whether AMPK pathway participates in MG-132-mediated myocardial protection in viral-induced myocarditis. METHODS ANDRESULTS:
Acute viral myocarditis models were established by intraperitoneal inoculation of CVB3 in male BALB/c mice. Myocarditis and age-matched control mice were administered MG-132 and/or BML-275 dihydrochloride (BML) (AMPK antagonist) intraperitoneally daily from the day following CVB3 inoculation. MG-132 improved hemodynamics and inhibited the structural remodeling of the ventricle in mice with myocarditis, while BML largely blunted these effects. TUNEL staining and immunochemistry suggested that MG-132 exerts anti-apoptotic and anti-inflammatory effects against CVB3-induced myocardial injuries. BML attenuated the effects of MG-132 on anti-apoptosis and anti-inflammation.CONCLUSION:
MG-132 modulated apoptosis and inflammation, improved hemodynamics, and inhibited the structural remodeling of ventricles in a myocarditis mouse model via regulation of the AMPK signal pathway.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Inibidores de Cisteína Proteinase
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Sistema de Sinalização das MAP Quinases
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Leupeptinas
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Miocardite
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article