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https://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 CENTRO- 07-ST24-FEDER-002008 info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID/NEU/04539/2013/PT |
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: | https://hdl.handle.net/10316/44844 | DOI: | 10.1016/j.bbadis.2017.07.030 | Rights: | openAccess |
Appears in Collections: | I&D CNC - Artigos em Revistas Internacionais |
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29_Coelho et al 2017_final.pdf | 3.9 MB | Adobe PDF | View/Open |
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