B-type natriuretic peptide protects cardiomyocytes at reperfusion via mitochondrial calcium uniporter.

B-type natriuretic peptide (BNP) is a regulatory autacoid in the mammalian myocardium, whose functions play significant roles in health and disease. Previous work has identified that BNP protect myocardium through mitochondrial pathway-dependent mechanism against ischemia-reperfusion (I/R) injury. Mitochondria are both essential effectors of cardioprotection and primary targets of cardioprotective signaling. In particular, mitochondrial channel are activated to act as the major determinants of cell life and death. Since the discovery of mitochondrial calcium uniporter (MCU), MCU has been its contribution to cardiomyocytes under specific physiological or pathological conditions. The role of mitochondria and MCU, in mediating reperfusion-induced heart injury is a novel investigative area. In addition, the relationship of BNP with MCU in cardiomyocytes undergoing reperfuison is unclear. In this study, we used cultured neonatal rat cardiomyocytes to investigate the effect of BNP on MCU during reperfusion, the well-characterized pathological process of heart diseases. Our results demonstrated that treatment with BNP protected cardiomyocytes from apoptosis against I/R injury. Further investigation of underlying mechanisms revealed that BNP could partly prevent opening of mitochondrial calcium uniporter during I/R. And these mechanisms were associated with BNP-attenuated dissipation of mitochondrial membrane potential (Deltapsi(m)), generation of reactive oxygen species (ROS). BNP also increased the level of anti-apoptotic Bcl-2 protein, decreased the expressions of pro-apoptotic Bax and Smac/DIABLO. In summary, we demonstrated that BNP exerts protective functions within reperfusion by blocking mitochondrial calcium uniporter. Our findings also suggested that phosphatidylinositol 3-kinase (PI3K) dependent pathway may be involved in the actions of BNP. Crown Copyright (c) 2009. Published by Elsevier SAS. All rights reserved.