Please use this identifier to cite or link to this item: http://hdl.handle.net/10316/44844
Title: Berberine-induced cardioprotection and Sirt3 modulation in doxorubicin-treated H9c2 cardiomyoblasts
Authors: Coelho, Ana R 
Martins, Tatiana R 
Couto, Renata 
Deus, Cláudia 
Pereira, Cláudia V 
Simões, Rui F 
Rizvanov, Albert A 
Silva, Filomena 
Cunha-Oliveira, Teresa 
Oliveira, Paulo J 
Serafim, Teresa L 
Issue Date: Nov-2017
Publisher: Elsevier
Project: info:eu-repo/grantAgreement/FCT/COMPETE/126115/PT 
PTDC/DTP-FTO/2433/ 2014 
POCI-01-0145-FEDER-016659 
POCI-01- 0145-FEDER-007440 
CENTRO- 07-ST24-FEDER-002008 
Serial title, monograph or event: Biochimica et biophysica acta
Volume: 1863
Issue: 11
Abstract: Doxorubicin (DOX) is one of the most widely used anti-neoplastic agents. However, treatment with DOX is associated with cumulative cardiotoxicity inducing progressive cardiomyocyte death. Sirtuin 3 (Sirt3), a mitochondrial deacetylase, regulates the activity of proteins involved in apoptosis, autophagy and metabolism. Our hypothesis is that pharmacological modulation by berberine (BER) pre-conditioning of Sirt3 protein levels decreases DOX-induced cardiotoxicity. Our results showed that DOX induces cell death in all experimental groups. Increase in Sirt3 content by transfection-mediated overexpression decreased DOX cytotoxicity, mostly by maintaining mitochondrial network integrity and reducing oxidative stress. p53 was upregulated by DOX, and appeared to be a direct target of Sirt3, suggesting that Sirt3-mediated protection against cell death could be related to this protein. BER pre-treatment increased Sirt3 and Sirt1 protein levels in the presence of DOX and inhibited DOX-induced caspase 9 and 3-like activation. Moreover, BER modulated autophagy in DOX-treated H9c2 cardiomyoblasts. Interestingly, mitochondrial biogenesis markers were upregulated in in BER/DOX-treated cells. Sirt3 over-expression contributes to decrease DOX cytotoxicity on H9c2 cardiomyoblasts, while BER can be used as a modulator of Sirtuin function and cell quality control pathways to decrease DOX toxicity.
URI: http://hdl.handle.net/10316/44844
Other Identifiers: 10.1016/j.bbadis.2017.07.030
DOI: 10.1016/j.bbadis.2017.07.030
Rights: openAccess
Appears in Collections:I&D CNC - Artigos em Revistas Internacionais

Files in This Item:
File Description SizeFormat
29_Coelho et al 2017_final.pdf3.9 MBAdobe PDFView/Open
Show full item record

SCOPUSTM   
Citations

13
checked on Feb 18, 2020

WEB OF SCIENCETM
Citations

14
checked on May 29, 2020

Page view(s) 50

494
checked on Jul 2, 2020

Download(s) 20

777
checked on Jul 2, 2020

Google ScholarTM

Check

Altmetric

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.