Astragaloside IV Inhibits Oxidative Stress-Induced Mitochondrial Permeability Transition Pore Opening by Inactivating GSK-3β via Nitric Oxide in H9c2 Cardiac Cells
Joint Authors
Jin, Yuanzhe
Zheng, Huan
Zhang, Yidong
He, Yonggui
Xu, Zhelong
Xi, Jinkun
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2012, Issue 2012 (31 Dec. 2012), pp.1-9, 9 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2012-09-25
Country of Publication
Egypt
No. of Pages
9
Main Subjects
Natural & Life Sciences (Multidisciplinary)
Biology
Abstract EN
Objective.
This study aimed to investigate whether astragaloside IV modulates the mitochondrial permeability transition pore (mPTP) opening through glycogen synthase kinase 3β (GSK-3β) in H9c2 cells.
Methods.
H9c2 cells were exposed to astragaloside IV for 20 min.
GSK-3β (Ser9), Akt (Ser473), and VASP (Ser239) activities were determined with western blot.
The mPTP opening was evaluated by measuring mitochondrial membrane potential (ΔΨm).
Nitric oxide (NO) generation was measured by 4-amino-5-methylamino-2′, 7′-difluorofluorescein (DAF-FM) diacetate.
Fluorescence images were obtained with confocal microscopy.
Results.
Astragaloside IV significantly enhanced GSK-3β phosphorylation and prevented H2O2-induced loss of ΔΨm.
These effects of astragaloside IV were reversed by the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002, the NO sensitive guanylyl cyclase selective inhibitor ODQ, and the PKG inhibitor KT5823.
Astragaloside IV activated Akt and PKG.
Astragaloside IV was also shown to increase NO production, an effect that was reversed by L-NAME and LY294002.
Astragaloside IV applied at reperfusion reduced cell death caused by simulated ischemia/reperfusion, indicating that astragaloside IV can prevent reperfusion injury.
Conclusions.
These data suggest that astragaloside IV prevents the mPTP opening and reperfusion injury by inactivating GSK-3β through the NO/cGMP/PKG signaling pathway.
NOS is responsible for NO generation and is activated by the PI3K/Akt pathway.
American Psychological Association (APA)
He, Yonggui& Xi, Jinkun& Zheng, Huan& Zhang, Yidong& Jin, Yuanzhe& Xu, Zhelong. 2012. Astragaloside IV Inhibits Oxidative Stress-Induced Mitochondrial Permeability Transition Pore Opening by Inactivating GSK-3β via Nitric Oxide in H9c2 Cardiac Cells. Oxidative Medicine and Cellular Longevity،Vol. 2012, no. 2012, pp.1-9.
https://search.emarefa.net/detail/BIM-509516
Modern Language Association (MLA)
He, Yonggui…[et al.]. Astragaloside IV Inhibits Oxidative Stress-Induced Mitochondrial Permeability Transition Pore Opening by Inactivating GSK-3β via Nitric Oxide in H9c2 Cardiac Cells. Oxidative Medicine and Cellular Longevity No. 2012 (2012), pp.1-9.
https://search.emarefa.net/detail/BIM-509516
American Medical Association (AMA)
He, Yonggui& Xi, Jinkun& Zheng, Huan& Zhang, Yidong& Jin, Yuanzhe& Xu, Zhelong. Astragaloside IV Inhibits Oxidative Stress-Induced Mitochondrial Permeability Transition Pore Opening by Inactivating GSK-3β via Nitric Oxide in H9c2 Cardiac Cells. Oxidative Medicine and Cellular Longevity. 2012. Vol. 2012, no. 2012, pp.1-9.
https://search.emarefa.net/detail/BIM-509516
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-509516