dc.contributor.author |
Coelho A. |
|
dc.contributor.author |
Martins T. |
|
dc.contributor.author |
Couto R. |
|
dc.contributor.author |
Deus C. |
|
dc.contributor.author |
Pereira C. |
|
dc.contributor.author |
Simões R. |
|
dc.contributor.author |
Rizvanov A. |
|
dc.contributor.author |
Silva F. |
|
dc.contributor.author |
Cunha-Oliveira T. |
|
dc.contributor.author |
Oliveira P. |
|
dc.contributor.author |
Serafim T. |
|
dc.date.accessioned |
2018-04-05T07:09:25Z |
|
dc.date.available |
2018-04-05T07:09:25Z |
|
dc.date.issued |
2017 |
|
dc.identifier.issn |
0925-4439 |
|
dc.identifier.uri |
http://dspace.kpfu.ru/xmlui/handle/net/129730 |
|
dc.description.abstract |
© 2017 Elsevier B.V. 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. |
|
dc.relation.ispartofseries |
Biochimica et Biophysica Acta - Molecular Basis of Disease |
|
dc.subject |
Berberine |
|
dc.subject |
Cardiotoxicity |
|
dc.subject |
Doxorubicin |
|
dc.subject |
Sirtuin 3 |
|
dc.title |
Berberine-induced cardioprotection and Sirt3 modulation in doxorubicin-treated H9c2 cardiomyoblasts |
|
dc.type |
Article |
|
dc.relation.ispartofseries-issue |
11 |
|
dc.relation.ispartofseries-volume |
1863 |
|
dc.collection |
Публикации сотрудников КФУ |
|
dc.relation.startpage |
2904 |
|
dc.source.id |
SCOPUS09254439-2017-1863-11-SID85030726008 |
|