MG-132 attenuates cardiac deterioration of viral myocarditis via AMPK pathway - 19/04/20
pages | 12 |
Iconographies | 9 |
Vidéos | 0 |
Autres | 0 |
Graphical abstract |
After viral infections, especially with CVB3, not only direct viral cytopathy but also activated host immune responses aggravate the deterioration of viral myocarditis during the acute phase. Through ubiquitin-proteasome system-meditated AMPK activation, MG-132, the proteasome inhibitor, inhibits viral replication, regulates mitochondrial-mediated intrinsic myocardial apoptosis, downregulates NF-κB-mediated inflammation and limits structural damage.
Highlights |
• | Direct viral cytopathy accompanied by excessively activated host immune responses aggravates the deterioration of viral myocarditis. |
• | The ubiquitin-proteasome system associates with viral replication and myocardial damage in Coxsackievirus B3-induced myocarditis. |
• | The ubiquitin-proteasome system-meditated AMPK activation inhibits viral replication and limits the virus-induced damage. |
• | Anti-inflammation and anti-apoptosis play a key role in ubiquitin-proteasome system-related cardiac protection. |
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 and results |
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.
Le texte complet de cet article est disponible en PDF.Keywords : CVB3, Myocarditis, MG-132, AMPK pathway, Inflammation, Apoptosis
Plan
Vol 126
Article 110091- juin 2020 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’achat d’article à l’unité est indisponible à l’heure actuelle.
Déjà abonné à cette revue ?