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Rui Simoes. Picture.

Rui Simoes

Rui Simöes, Guest researcher

Rui Simoes. Picture.

Berberine-induced cardioprotection and Sirt3 modulation in doxorubicin-treated H9c2 cardiomyoblasts

Author

  • Ana R Coelho
  • Tatiana R Martins
  • Renata Couto
  • Cláudia Deus
  • Cláudia V Pereira
  • Rui F Simões
  • Albert A Rizvanov
  • Filomena Silva
  • Teresa Cunha-Oliveira
  • Paulo J Oliveira
  • Teresa L Serafim

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