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
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.
Peer review: yes
URI: http://hdl.handle.net/10316/44844
DOI: 10.1016/j.bbadis.2017.07.030
Publisher Version: http://www.sciencedirect.com/science/article/pii/S092544391730265X
Appears in Collections:I&D CNC - Artigos em Revistas Internacionais

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