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https://hdl.handle.net/10316/108385
Título: | Involvement of the p62/NRF2 signal transduction pathway on erythrophagocytosis | Autor: | Santarino, Inês Viegas, Michelle Domingues, Neuza S. Ribeiro, Ana M. Soares, Miguel P. Vieira, Otília V. |
Data: | 19-Jul-2017 | Editora: | Springer Nature | Projeto: | This work was supported by the Foundation for Science and Technology of the Portuguese Ministry of Science and Higher Education [HMSP-ICT/0024/2010, co-founded by the European Union (FEDER – Fundo Europeu de Desenvolvimento Regional) through COMPETE – Programa Operacional Factores de Competitividade and QREN – Quadro de Referência Estratégico], iNOVA4Health - UID/Multi/04462/2013, a program financially supported by FCT through national funds and co-funded by FEDER under the PT2020 Partnership Agreement and FCT to OVV. PhD fellowships SFRH/BD/62197/2009, SFRH/BD/90258/2012 and SFRH /BD/51877/2012 and SFRH/BD/52293/2013. PTDC/SAU-TOX/116627/2010, HMSP-ICT/0022/2010, European Community 7th Framework Grant ERC-2011-AdG 294709-DAMAGECONTROL to MPS | Título da revista, periódico, livro ou evento: | Scientific Reports | Volume: | 7 | Número: | 1 | Resumo: | Erythrophagocytosis, the phagocytic removal of damaged red blood cells (RBC), and subsequent phagolysosome biogenesis are important processes in iron/heme metabolism and homeostasis. Phagolysosome biogenesis implies the interaction of nascent phagosomes with endocytic compartments and also autophagy effectors. Here, we report that besides recruitment of microtubule-associated protein-1-light chain 3 (LC3), additional autophagy machinery such as sequestosome 1 (p62) is also acquired by single-membrane phagosomes at very early stages of the phagocytic process and that its acquisition is very important to the outcome of the process. In bone marrow-derived macrophages (BMDM) silenced for p62, RBC degradation is inhibited. P62, is also required for nuclear translocation and activation of the transcription factor Nuclear factor E2-related Factor 2 (NRF2) during erythrophagocytosis. Deletion of the Nrf2 allele reduces p62 expression and compromises RBC degradation. In conclusion, we reveal that erythrophagocytosis relies on an interplay between p62 and NRF2, potentially acting as protective mechanism to maintain reactive oxygen species at basal levels and preserve macrophage homeostasis. | URI: | https://hdl.handle.net/10316/108385 | ISSN: | 2045-2322 | DOI: | 10.1038/s41598-017-05687-1 | Direitos: | openAccess |
Aparece nas coleções: | I&D CNC - Artigos em Revistas Internacionais |
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s41598-017-05687-1.pdf | 6.24 MB | Adobe PDF | Ver/Abrir |
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