Abstract 257: Berbamine Postconditioning Protects the Heart From Ischemia/Reperfusion Injury Through the Regulation of Autophagy During Reperfusion
Myocardial infarction resulting from coronary atherosclerosis is the leading cause of death in modern society. Reperfusion is an essential treatment to salvage ischemia myocardium from necrosis, while it also leads to additional damage. Therefore, exploring effective medicines to protect the heart from post-ischemic injury is one of the major objectives of cardiovascular research. Berbamine, a nature compound of bisbenzylisochinoline alkaloids from Barberry, protects the heart from ischemia/reperfusion (I/R) injury when given before I/R, but it is unknown whether it has cardioprotective effects when given at the onset of reperfusion (postconditioning, PoC), a protocol with more clinical impact. Therefore, the present study was designed to determine whether berbamine PoC (BMPoC) is able to protect the heart from reperfusion injury by using perfused I/R rat hearts and simulated I/R cardiomyocytes. We found that BMPoC added during the first 5-min of reperfusion concentration-dependently improved post-ischemic myocardial function and limited infarcted area. A similar protection was observed in isolated rat cardiomyocytes characterized by the attenuation of I/R-induced depression of cell contraction and loss of mitochondrial membrane potential. Moreover, autophagy (an intracellular bulk degradation process for proteins and organelles) was significantly stimulated by myocardial I/R, but it was suppressed by BMPoC. Next, we examined how berbamine regulates autophagy and found that BMPoC inhibited the expression of beclin 1, a critical regulator for autophagosome initiation. Then, adenoviral overexpression and knockdown of beclin 1 in ventricles conformed its roles in the BMPoC-mediated cardioprotection. Further, Western blot analysis revealed that BMPoC-suppressed beclin 1 expression was mediated via the activation of PI3K/Akt signaling pathway. Our results suggest that BMPoC confers cardioprotection against I/R injury at least in part by the inhibition of beclin1-dependent autophagy through the activation of PI3K/Akt signaling pathway. These findings reveal new roles and mechanisms of berbamine in the cardioprotection against I/R injury.
Author Disclosures: Y. Zheng: None. X. Li: None. J. Wang: None. J. Tan: None. C. Zhang: None. H. Yang: None.
- © 2015 by American Heart Association, Inc.