Utilize este identificador para referenciar este registo: http://hdl.handle.net/10400.7/778
Título: Involvement of the p62/NRF2 signal transduction pathway on erythrophagocytosis
Autor: Santarino, Inês B.
Viegas, Michelle S.
Domingues, Neuza S.
Ribeiro, Ana M.
Soares, Miguel P.
Vieira, Otília V.
Palavras-chave: Phagocytosis
Sickle cell disease
Data: 19-Jul-2017
Editora: Nature Publishing Group
Citação: Santarino, I. B. et al. Involvement of the p62/NRF2 signal transduction pathway on erythrophagocytosis. Sci Rep 7, 5812 (2017).
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.
Descrição: This deposit is composed by the main article plus the supplementary materials of the publication.
Peer review: yes
URI: http://hdl.handle.net/10400.7/778
DOI: 10.1038/s41598-017-05687-1
Versão do Editor: https://www.nature.com/articles/s41598-017-05687-1
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Santarino_SciRep_2017_7(1)_ESM.pdfsupplementary material278,61 kBAdobe PDFVer/Abrir


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