Berberine-induced cardioprotection and Sirt3 modulation in doxorubicin-treated H9c2 cardiomyoblasts
العنوان: | Berberine-induced cardioprotection and Sirt3 modulation in doxorubicin-treated H9c2 cardiomyoblasts |
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المؤلفون: | Teresa Cunha-Oliveira, Claudia V. Pereira, Rui F. Simões, Filomena S. G. Silva, Tatiana R. Martins, Renata Couto, Teresa L. Serafim, Paulo J. Oliveira, Ana R Coelho, Albert A. Rizvanov, Cláudia M. Deus |
المصدر: | Repositório Científico de Acesso Aberto de Portugal Repositório Científico de Acesso Aberto de Portugal (RCAAP) instacron:RCAAP |
بيانات النشر: | Elsevier, 2017. |
سنة النشر: | 2017 |
مصطلحات موضوعية: | 0301 basic medicine, Programmed cell death, Cardiotonic Agents, Berberine, SIRT3, Muscle Proteins, macromolecular substances, Biology, Pharmacology, medicine.disease_cause, Cell Line, 03 medical and health sciences, Sirtuin 3, medicine, polycyclic compounds, Humans, Molecular Biology, Cardiotoxicity, organic chemicals, Autophagy, technology, industry, and agriculture, 3. Good health, carbohydrates (lipids), Oxidative Stress, 030104 developmental biology, Mitochondrial biogenesis, Doxorubicin, Apoptosis, Sirtuin, biology.protein, Cancer research, Molecular Medicine, Myoblasts, Cardiac, Oxidative stress |
الوصف: | 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. FCT |
اللغة: | English |
الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7b5f399e26ac0b5dd4f47467284c3185Test https://hdl.handle.net/10316/44844Test |
حقوق: | OPEN |
رقم الانضمام: | edsair.doi.dedup.....7b5f399e26ac0b5dd4f47467284c3185 |
قاعدة البيانات: | OpenAIRE |
الوصف غير متاح. |