Abstract 275: Berbamine Confers Cardioprotection Against Ischemia-Reperfusion Injury by Attenuating Ca 2+ Overload and Preventing Calpain Activation Through Protection of Mitochondria

Abstract

Reperfusion is an essential treatment to salvage ischemia myocardium from necrosis. However, the reperfusion can also lead to additional damage. Ischemic preconditioning is a powerful way to initiate intrinsic adaptive responses protecting the heart from subsequent severe ischemia/reperfusion (I/R) injury that can be mimicked by pharmacological preconditioning. However, so far few agents are clinically available for patients with ischemia heart disease. There is a growing interest in exploring effective cardioprotective components extracted from Traditional Chinese Medicine because they have been practiced for thousands of years, providing a vast source of pharmaceutical materials. Berbamine, a kind of bisbenzylisochinoline alkaloids derived from the roots, barks and stems of Barberry , was reported to protect myocardium from ischemia/reperfusion (I/R) injury, but the underlying mechanisms are largely unknown. Here, we investigated whether berbamine confers cardioprotection via preventing calpain activation and protein degradation. We identified here that berbamine pretreatment from 10 to 100 nM concentration-dependently improved post-ischemic myocardial function in isolated Sprague-Dawley rat hearts subjected to 30 min ischemia/45 min reperfusion. Similar protection was confirmed in isolated cardiomyocytes characterized by the attenuation of I/R-induced intracellular Ca 2+ overloading and the depression of Ca 2+ transients and cell shortening. Moreover, I/R-induced decreases of Ca 2+ handling proteins were significantly attenuated by berbamine. Further analysis showed that those protections were related to the suppression of I/R-induced calpain activity and the protection of mitochondrial function by berbamine. These findings suggest that berbamine confers cardioprotections against I/R injury by attenuating Ca 2+ overloading and preventing calpain activation; and the protection of mitochondria is critical for the cardioprotection.