Berberine Ameliorates Doxorubicin-Induced Cardiotoxicity via a SIRT1p66Shc-Mediated Pathway
Joint Authors
Wu, Yan-Zhao
Zhang, Lan
Wu, Zi-Xiao
Shan, Tong-tong
Xiong, Chen
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-14, 14 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-12-06
Country of Publication
Egypt
No. of Pages
14
Main Subjects
Abstract EN
Doxorubicin- (DOX-) induced cardiotoxicity is associated with oxidative stress and cardiomyocyte apoptosis.
The adaptor protein p66Shc regulates the cellular redox status and determines cell susceptibility to apoptosis.
This study is aimed at investigating the involvement of sirtuin 1- (SIRT1-) mediated p66Shc inhibition in DOX-induced redox signalling and exploring the possible protective mechanisms of berberine (Ber) against DOX-triggered cardiac injury in rats and a cultured H9c2 cell line.
Our results showed that the Ber pretreatment markedly increased CAT, SOD, and GSH-PX activities, decreased the levels of MDA, and improved the electrocardiogram and histopathological changes in the myocardium in DOX-treated rats (in vivo).
Furthermore, Ber significantly ameliorated the DOX-induced oxidative insult and mitochondrial damage by adjusting the levels of intracellular ROS, ΔΨm, and [Ca2+]m in H9c2 cells (in vitro).
Importantly, the Ber pretreatment increased SIRT1 expression following DOX exposure but downregulated p66Shc.
Consistent with the results demonstrating the SIRT1-mediated inhibition of p66Shc expression, the Ber pretreatment inhibited DOX-triggered cardiomyocyte apoptosis and mitochondrial dysfunction.
After exposing H9c2 cells to DOX, the increased SIRT1 expression induced by Ber was abrogated by a SIRT1-specific inhibitor (EX527) or the use of siRNA against SIRT1.
Accordingly, SIRT1 inhibition significantly abrogated the suppression of p66Shc expression and protection of Ber against DOX-induced oxidative stress and apoptosis.
These results suggest that Ber protects the heart from DOX injury through SIRT1-mediated p66Shc suppression, offering a novel mechanism responsible for the protection of Ber against DOX-induced cardiomyopathy.
American Psychological Association (APA)
Wu, Yan-Zhao& Zhang, Lan& Wu, Zi-Xiao& Shan, Tong-tong& Xiong, Chen. 2019. Berberine Ameliorates Doxorubicin-Induced Cardiotoxicity via a SIRT1p66Shc-Mediated Pathway. Oxidative Medicine and Cellular Longevity،Vol. 2019, no. 2019, pp.1-14.
https://search.emarefa.net/detail/BIM-1202532
Modern Language Association (MLA)
Wu, Yan-Zhao…[et al.]. Berberine Ameliorates Doxorubicin-Induced Cardiotoxicity via a SIRT1p66Shc-Mediated Pathway. Oxidative Medicine and Cellular Longevity No. 2019 (2019), pp.1-14.
https://search.emarefa.net/detail/BIM-1202532
American Medical Association (AMA)
Wu, Yan-Zhao& Zhang, Lan& Wu, Zi-Xiao& Shan, Tong-tong& Xiong, Chen. Berberine Ameliorates Doxorubicin-Induced Cardiotoxicity via a SIRT1p66Shc-Mediated Pathway. Oxidative Medicine and Cellular Longevity. 2019. Vol. 2019, no. 2019, pp.1-14.
https://search.emarefa.net/detail/BIM-1202532
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1202532