Unacylated ghrelin analog prevents myocardial reperfusion injury independently of permeability transition pore.
Basic Res Cardiol
; 112(1): 4, 2017 01.
Article
en En
| MEDLINE
| ID: mdl-27995363
ABSTRACT
Reperfusion injury is responsible for an important part of myocardial infarct establishment due notably to triggering cardiomyocytes death at the first minutes of reperfusion. AZP-531 is an optimized analog of unacylated ghrelin currently in clinical development in several metabolic diseases. We investigated a potential cardioprotective effect of AZP-531 in ischemia/reperfusion (IR) and the molecular underlying mechanism(s) involved in this protection. In vivo postconditioning with AZP-531 in C57BL6 mouse IR model decreased infarct size. Western blot analysis on areas at risk from the different mouse groups showed that AZP-531 activates Akt, ERK1-2 as well as S6 and 4EBP1, mTORC1 effectors. We also showed an inhibition of caspase 3 cleavage and Bax translocation to the mitochondria. AZP-531 also stimulated the expression of antioxidants and was capable of decreasing mitochondrial H2O2 production, contributing to the reduction of ROS accumulation. AZP-531 exhibits cardioprotective effect when administrated for postconditioning in C57BL6 mouse IR model. Treatment with AZP-531 rescued the myocardium from cell death at early reperfusion by stimulating protein synthesis, inhibiting Bax/caspase 3-induced apoptosis as well as ROS accumulation and oxidative stress-induced necrosis. AZP-531 may prove useful in the treatment of IR injury.
Palabras clave
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Fragmentos de Péptidos
/
Péptidos Cíclicos
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Daño por Reperfusión Miocárdica
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Miocitos Cardíacos
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Ghrelina
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Poscondicionamiento Isquémico
Límite:
Animals
Idioma:
En
Revista:
Basic Res Cardiol
Año:
2017
Tipo del documento:
Article
País de afiliación:
Francia