Please use this identifier to cite or link to this item:
https://hdl.handle.net/10316/88473
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Ferreira, Luciana L | - |
dc.contributor.author | Cervantes, Marlene | - |
dc.contributor.author | Froufe, Hugo J. C. | - |
dc.contributor.author | Egas, Conceição | - |
dc.contributor.author | Cunha-Oliveira, Teresa | - |
dc.contributor.author | Sassone-Corsi, Paolo | - |
dc.contributor.author | Oliveira, Paulo J. | - |
dc.date.accessioned | 2019-12-15T14:29:22Z | - |
dc.date.available | 2019-12-15T14:29:22Z | - |
dc.date.issued | 2019-11-25 | - |
dc.identifier.issn | 0340-5761 | pt |
dc.identifier.issn | 1432-0738 | pt |
dc.identifier.uri | https://hdl.handle.net/10316/88473 | - |
dc.description.abstract | Circadian rhythms disruption can be the cause of chronic diseases. External cues, including therapeutic drugs, have been shown to modulate peripheral-circadian clocks. Since anthracycline cardiotoxicity is associated with loss of mitochondrial function and metabolic remodeling, we investigated whether the energetic failure induced by sub-chronic doxorubicin (DOX) treatment in juvenile mice was associated with persistent disruption of circadian regulators. Juvenile C57BL/6J male mice were subjected to a sub-chronic DOX treatment (4 weekly injections of 5 mg/kg DOX) and several cardiac parameters, as well as circadian-gene expression and acetylation patterns, were analyzed after 6 weeks of recovery time. Complementary experiments were performed with Mouse Embryonic Fibroblasts (MEFs) and Human Embryonic Kidney 293 cells. DOX-treated juvenile mice showed cardiotoxicity markers and persistent alterations of transcriptional- and signaling cardiac circadian homeostasis. The results showed a delayed influence of DOX on gene expression, accompanied by changes in SIRT1-mediated cyclic deacetylation. The mechanism behind DOX interference with the circadian clock was further studied in vitro, in which were observed alterations of circadian-gene expression and increased BMAL1 SIRT1-mediated deacetylation. In conclusion, DOX treatment in juvenile mice resulted in disruption of oscillatory molecular mechanisms including gene expression and acetylation profiles. | pt |
dc.language.iso | eng | pt |
dc.rights | embargoedAccess | pt |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | pt |
dc.subject | Cardiotoxicity; Chemotherapy; Circadian clock; Doxorubicin; Mitochondria; Protein acetylation | pt |
dc.title | Doxorubicin persistently rewires cardiac circadian homeostasis in mice | pt |
dc.type | article | - |
degois.publication.title | Archives of Toxicology | pt |
dc.relation.publisherversion | https://link.springer.com/article/10.1007%2Fs00204-019-02626-z | pt |
dc.peerreviewed | yes | pt |
dc.identifier.doi | 10.1007/s00204-019-02626-z | pt |
dc.date.embargo | 2020-11-24 | * |
uc.date.periodoEmbargo | 365 | pt |
item.openairetype | article | - |
item.fulltext | Com Texto completo | - |
item.languageiso639-1 | en | - |
item.grantfulltext | open | - |
item.cerifentitytype | Publications | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
crisitem.author.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.orcid | 0000-0002-7382-0339 | - |
crisitem.author.orcid | 0000-0002-5201-9948 | - |
Appears in Collections: | I&D CNC - Artigos em Revistas Internacionais |
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File | Description | Size | Format | |
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38_Ferreira-2019.pdf | 4.22 MB | Adobe PDF | View/Open |
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