Harisseh 2017 Basic Res Cardiol
|Harisseh R, Pillot B, Gharib A, Augeul L, Gallo-Bona N, Ferrera R, Loufouat J, Delale T, Allas S, Abribat T, Crola Da Silva C, Ovize M (2017) Unacylated ghrelin analog prevents myocardial reperfusion injury independently of permeability transition pore. Basic Res Cardiol 112:4.|
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.
• Keywords: Bax/Caspase 3 apoptosis, Cardiomyocyte, In vivo Ischemia–Reperfusion, Mitochondria, Oxidative stress, Unacylated ghrelin, Amplex Red
• O2k-Network Lab: FR Lyon Ovize M
Labels: MiParea: Respiration
Stress:Ischemia-reperfusion, Permeability transition Organism: Mouse Tissue;cell: Heart Preparation: Permeabilized cells
Coupling state: OXPHOS, ET Pathway: N, S, CIV, ROX HRR: Oxygraph-2k