Erratum: A novel AMPK activator from Chinese herb medicine and ischemia phosphorylate the cardiac transcription factor FOXO3.
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 Thr(172) phosphorylation, as well as phosphorylation of downstream FOXO3 (Ser(413)) 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 (Ser(413)) 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.[This corrects the article on p. 116 in vol. 1, PMID: 20445824.].
Division of Pharmaceutical Sciences & Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, School of Pharmacy Laramie, WY 82071.
Jingying
J
Wang
Division of Pharmaceutical Sciences & Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, School of Pharmacy Laramie, WY 82071.
Heng
H
Ma
Institute of Physiology, School of Basic Medical Sciences, Lanzhou University Lanzhou 730000, P.R. China.
Xiaoyu
X
Zhang
Division of Pharmaceutical Sciences & Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, School of Pharmacy Laramie, WY 82071.
Leilei
L
He
Department of Research & Development, Kanghong Pharmaceutical Co. Ltd Chengdu 610000, P.R. China.
Jianming
J
Wu
Department of Research & Development, Kanghong Pharmaceutical Co. Ltd Chengdu 610000, P.R. China.
Xiaoping
X
Gao
Division of Pharmaceutical Sciences & Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, School of Pharmacy Laramie, WY 82071.
Jun
J
Ren
Division of Pharmaceutical Sciences & Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, School of Pharmacy Laramie, WY 82071.
Ji
J
Li
AMP-activated protein kinase (AMPK); forkhead transcription factor 3 (FOXO3); ischemia; oleanolic acid (OA)