Plant Natural Product Formononetin Protects Rat Cardiomyocyte H9c2 Cells against Oxygen Glucose Deprivation and Reoxygenation via Inhibiting ROS Formation and Promoting GSK-3β Phosphorylation
Joint Authors
Han, Yifan
Cheng, Yuanyuan
Xia, Zhengyuan
Rong, Jianhui
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2016, Issue 2016 (31 Dec. 2016), pp.1-11, 11 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2016-01-06
Country of Publication
Egypt
No. of Pages
11
Main Subjects
Abstract EN
The opening of mitochondrial permeability transition pore (mPTP) is a major cause of cell death in ischemia reperfusion injury.
Based on our pilot experiments, plant natural product formononetin enhanced the survival of rat cardiomyocyte H9c2 cells during oxygen glucose deprivation (OGD) and reoxygenation.
For mechanistic studies, we focused on two major cellular factors, namely, reactive oxygen species (ROS) and glycogen synthase kinase 3β (GSK-3β), in the regulation of mPTP opening.
We found that formononetin suppressed the formation of ROS and superoxide in a concentration-dependent manner.
Formononetin also rescued OGD/reoxygenation-induced loss of mitochondrial membrane integrity.
Further studies suggested that formononetin induced Akt activation and GSK-3β (Ser9) phosphorylation, thereby reducing GSK-3β activity towards mPTP opening.
PI3K and PKC inhibitors abolished the effects of formononetin on mPTP opening and GSK-3β phosphorylation.
Immunoprecipitation experiments further revealed that formononetin increased the binding of phosphor-GSK-3β to adenine nucleotide translocase (ANT) while it disrupted the complex of ANT with cyclophilin D.
Moreover, immunofluorescence revealed that phospho-GSK-3β (Ser9) was mainly deposited in the space between mitochondria and cell nucleus.
Collectively, these results indicated that formononetin protected cardiomyocytes from OGD/reoxygenation injury via inhibiting ROS formation and promoting GSK-3β phosphorylation.
American Psychological Association (APA)
Cheng, Yuanyuan& Xia, Zhengyuan& Han, Yifan& Rong, Jianhui. 2016. Plant Natural Product Formononetin Protects Rat Cardiomyocyte H9c2 Cells against Oxygen Glucose Deprivation and Reoxygenation via Inhibiting ROS Formation and Promoting GSK-3β Phosphorylation. Oxidative Medicine and Cellular Longevity،Vol. 2016, no. 2016, pp.1-11.
https://search.emarefa.net/detail/BIM-1113677
Modern Language Association (MLA)
Cheng, Yuanyuan…[et al.]. Plant Natural Product Formononetin Protects Rat Cardiomyocyte H9c2 Cells against Oxygen Glucose Deprivation and Reoxygenation via Inhibiting ROS Formation and Promoting GSK-3β Phosphorylation. Oxidative Medicine and Cellular Longevity No. 2016 (2016), pp.1-11.
https://search.emarefa.net/detail/BIM-1113677
American Medical Association (AMA)
Cheng, Yuanyuan& Xia, Zhengyuan& Han, Yifan& Rong, Jianhui. Plant Natural Product Formononetin Protects Rat Cardiomyocyte H9c2 Cells against Oxygen Glucose Deprivation and Reoxygenation via Inhibiting ROS Formation and Promoting GSK-3β Phosphorylation. Oxidative Medicine and Cellular Longevity. 2016. Vol. 2016, no. 2016, pp.1-11.
https://search.emarefa.net/detail/BIM-1113677
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1113677