Exogenous spermine inhibits hypoxia/ischemia-induced myocardial apoptosis via regulation of mitochondrial permeability transition pore and associated pathways:

摘要: Myocardial infarction (MI) is associated with a high mortality rate, which attributed to the effects of myocyte loss that occurs as result ischemia-induced cell death. Very few therapies can effectively prevent or delay ischemia. Polyamines (PAs) are polycations required for growth and division, their use may loss. The aim this study was investigate relationship between hypoxia/ischemia (H/I)-induced apoptosis PA metabolism ability spermine limit H/I injury in cardiomyocytes by blocking mitochondrial apoptotic pathway. Neonatal rat were placed under hypoxic conditions 24 h after being subjected 5 μM pretreatment therapy. induced catabolism, indicated 1.3-fold up-regulation spermidine/spermine N(1)-acetyltransferase expression. Exogenous significantly reduced H/I-induced death rate (60 ± 2 36 ± 2%) (42 ± 2 21 ± 2%); it also attenuated lactate dehyodrogenase creatine kinase leakage (440 ± 13 336 ± 16 U/L 275 ± 15 235 ± 13 U/L). Furthermore, decreases calcium overload (3.8 ± 0.2 2.2 ± 0.1 a.u.). Moreover, remarkably decreased cytochrome c release from mitochondria cytosol, lowering expression cleaved caspase-3 -9. With pretreatment, there an increase Bcl-2 levels phosphorylation ERK1/2, phosphoinositide 3-kinase, Akt, GSK-3β, preserving membrane potential inducing permeability transition pore opening. In conclusion, endogenous concentrations cardiomyocytes, ultimately apoptosis. addition exogenous prevented