A novel AMPK activator from Chinese herb medicine and ischemia phosphorylate the cardiac transcription factor FOXO3

International Journal of Physiology, Pathophysiology and Pharmacology

Xiaoyu Zhang¹  Jianming Wu¹  Xiaoping Gao¹  Heng Ma¹  Jingying Wang¹  Jun Ren¹  Leilei He¹  Ji Li¹ 

关键词: AMP-activated protein kinase (AMPK);    ischemia;    Forkhead transcription factor 3 (FOXO3);    Oleanolic Acid (OA);   

DOI  :  

学科分类：生理学与病理学

来源: e-Century Publishing Corporation

【 摘 要 】

Oleanolic Acid (OA) is a nature product extracted from Chinese Herb Medicine which is traditionally used as treatment of diabetes and ischemic heart diseases. Mounting evidence showed that AMP-activated protein kinase (AMPK) has cardioprotective effect against ischemic injury and the forkhead transcription factor 3 (FOXO3) was recently identified as a downstream target of AMPK. We hypothesize that OA may protect against ischemic dysfunction of cardiomyocytes via activation of AMPK signaling pathway. Male C57BL/6 mice which were subjected to in vivo regional cardiac ischemia stimulated AMPK Thr¹⁷² phosphorylation, as well as phosphorylation of downstream FOXO3 (Ser⁴¹³) and acetyl CoA carboxylase (ACC). The natural product, OA, significantly stimulated cardiac AMPK activation in cardiomyocyes in time- and dose-dependent manners. The mechanism of AMPK activation by OA may be due to the loss mitochondrial membrane potential (ΔΨm) as shown by JC-1 fluorescence assay. Intriguingly, OA as an AMPK activator also triggered FOXO3 (Ser⁴¹³) phosphorylation in cardiomyocytes. Furthermore, OA treatment can protect cardiomyocytes from contractile dysfunction induced by hypoxia. Taken together, the results indicated that both ischemia and OA stimulated cardiac AMPK phosphorylation, as well downstream FOXO3 phosphorylation. The cardioprotective effect of OA maybe associated with activation of AMPK signaling pathways.

【 授权许可】

Unknown