RRC ID |
48890
|
著者 |
Santarino IB, Viegas MS, Domingues NS, Ribeiro AM, Soares MP, Vieira OV.
|
タイトル |
Involvement of the p62/NRF2 signal transduction pathway on erythrophagocytosis.
|
ジャーナル |
Sci Rep
|
Abstract |
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.
|
巻・号 |
7(1)
|
ページ |
5812
|
公開日 |
2017-7-19
|
DOI |
10.1038/s41598-017-05687-1
|
PII |
10.1038/s41598-017-05687-1
|
PMID |
28724916
|
PMC |
PMC5517431
|
MeSH |
Animals
Autophagy
Cell Line
Erythrocytes / cytology*
Erythrocytes / metabolism*
Gene Expression Regulation
Humans
Intracellular Space / metabolism
Mice, Inbred C57BL
Mice, Knockout
Microtubule-Associated Proteins
NF-E2-Related Factor 2 / metabolism*
Phagocytosis*
Phagosomes / metabolism
Phosphorylation
Rabbits
Sequestosome-1 Protein / metabolism*
Signal Transduction*
Ubiquitin / metabolism
|
IF |
3.998
|
引用数 |
7
|
リソース情報 |
実験動物マウス |
RBRC01390 |