berberine inhibits doxorubicin-triggered cardiomyocyte apoptosis via attenuating mitochondrial dysfunction and increasing bcl-2 expression小檗碱通过衰减抑制doxorubicin-triggered心肌细胞凋亡的线粒体功能障碍和增加bcl - 2表达.pdfVIP

Berberine Inhibits Doxorubicin-Triggered Cardiomyocyte Apoptosis via Attenuating Mitochondrial Dysfunction and Increasing Bcl-2 Expression 1 1 1 1 1 1 1,2 Xiuxiu Lv , Xiaohui Yu , Yiyang Wang , Faqiang Wang , Hongmei Li , Yanping Wang , Daxiang Lu , Renbin Qi1,2, Huadong Wang1,2* 1 Department of Pathophysiology, School of Medicine, Jinan University, Guangzhou, Guangdong, China, 2 Key Laboratory of State Administration of Traditional Chinese Medicine of the People’s Republic of China, School of Medicine, Jinan University, Guangzhou, Guangdong, China Abstract Cardiomyocyte apoptosis is an important event in doxorubicin (DOX)-induced cardiac injury. The aim of the present study was to investigate the protection of berberine (Ber) against DOX- triggered cardiomyocyte apoptosis in neonatal rat cardiomyocytes and rats. In neonatal rat cardiomyocytes, Ber attenuated DOX-induced cellular injury and apoptosis in a dose-dependent manner. However, Ber has no significant effect on viability of MCF-7 breast cancer cells treated with DOX. Ber reduced caspase-3 and caspase-9, but not caspase-8 activity in DOX-treated cardiomyocytes. Furthermore, Ber decreased adenosine monophosphate-activated protein kinase a (AMPKa) and p53 phosphorylation at 2 h, cytosolic cytochrome c and mitochondrial Bax levels and increased Bcl-2 level at 6 h in DOX-stimulated cardiomyocytes. Pretreatment with compound C, an AMPK inhibitor, also suppressed p53 phosphorylation and apoptosis in DOX-treated cardiomyocytes. DOX stimulation for 30 min led to a loss of mitochondrial membrane potential and a rise in the AMP/ATP ratio. Ber markedly