
Rui Simoes
Rui Simöes, Guest researcher

Berberine-induced cardioprotection and Sirt3 modulation in doxorubicin-treated H9c2 cardiomyoblasts
Author
Summary, in English
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.
Publishing year
2017-11
Language
English
Pages
2904-2923
Publication/Series
Biochimica et Biophysica Acta - Molecular Basis of Disease
Volume
1863
Issue
11
Document type
Journal article
Publisher
Elsevier
Keywords
- Berberine/pharmacology
- Cardiotonic Agents/pharmacology
- Cell Line
- Doxorubicin/adverse effects
- Humans
- Muscle Proteins/metabolism
- Myoblasts, Cardiac/enzymology
- Oxidative Stress/drug effects
- Sirtuin 3/metabolism
Status
Published
ISBN/ISSN/Other
- ISSN: 0925-4439