A novel AMPK activator from Chinese herb medicine and ischemiaphosphorylate 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 Medicinewhich is traditionally used as treatment of diabetes and ischemic heartdiseases. Mounting evidence showed that AMP-activated protein kinase (AMPK) hascardioprotective effect against ischemic injury and the forkhead transcriptionfactor 3 (FOXO3) was recently identified as a downstream target of AMPK. Wehypothesize that OA may protect against ischemic dysfunction of cardiomyocytesvia activation of AMPK signaling pathway. Male C57BL/6 mice which were subjectedto in vivo regional cardiac ischemia stimulated AMPKThr¹⁷² phosphorylation, as well as phosphorylation of downstreamFOXO3 (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 tothe loss mitochondrial membrane potential (ΔΨm) as shown by JC-1fluorescence assay. Intriguingly, OA as an AMPK activator also triggered FOXO3(Ser⁴¹³) phosphorylation in cardiomyocytes. Furthermore, OAtreatment can protect cardiomyocytes from contractile dysfunction induced byhypoxia. Taken together, the results indicated that both ischemia and OAstimulated cardiac AMPK phosphorylation, as well downstream FOXO3phosphorylation. The cardioprotective effect of OA maybe associated withactivation of AMPK signaling pathways.

【 授权许可】

Unknown