Berberine-induced cardioprotection and Sirt3 modulation in doxorubicin-treated H9c2 cardiomyoblasts
(2017) In Biochimica et Biophysica Acta - Molecular Basis of Disease 1863(11). p.2904-2923- 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... (More)
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.
(Less)
- author
- publishing date
- 2017-11
- type
- Contribution to journal
- publication status
- published
- 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
- in
- Biochimica et Biophysica Acta - Molecular Basis of Disease
- volume
- 1863
- issue
- 11
- pages
- 2904 - 2923
- publisher
- Elsevier
- external identifiers
-
- scopus:85030726008
- pmid:28760703
- ISSN
- 0925-4439
- DOI
- 10.1016/j.bbadis.2017.07.030
- language
- English
- LU publication?
- no
- id
- 811338f8-4c28-4684-aa7a-eb68da526e12
- date added to LUP
- 2021-09-21 19:24:53
- date last changed
- 2024-03-23 10:14:34
@article{811338f8-4c28-4684-aa7a-eb68da526e12, abstract = {{<p>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.</p>}}, author = {{Coelho, Ana R and Martins, Tatiana R and Couto, Renata and Deus, Cláudia and Pereira, Cláudia V and Simões, Rui F and Rizvanov, Albert A and Silva, Filomena and Cunha-Oliveira, Teresa and Oliveira, Paulo J and Serafim, Teresa L}}, issn = {{0925-4439}}, 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}}, language = {{eng}}, number = {{11}}, pages = {{2904--2923}}, publisher = {{Elsevier}}, series = {{Biochimica et Biophysica Acta - Molecular Basis of Disease}}, title = {{Berberine-induced cardioprotection and Sirt3 modulation in doxorubicin-treated H9c2 cardiomyoblasts}}, url = {{http://dx.doi.org/10.1016/j.bbadis.2017.07.030}}, doi = {{10.1016/j.bbadis.2017.07.030}}, volume = {{1863}}, year = {{2017}}, }