Iron deficiency induces autophagy and activates Nrf2 signal through modulating p62/SQSTM
| Autor: | Mariko Uehara, Hirofumi Inoue, Nobuyuki Takahashi, Shin-ichi Katsumata, Rie Katsumata-Tsuboi, Nobuaki Hanawa |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
chemistry.chemical_classification Sequestosome-1 Protein Reactive oxygen species Autophagy General Medicine medicine.disease_cause General Biochemistry Genetics and Molecular Biology Cell biology Deferoxamine 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Aggresome chemistry 030220 oncology & carcinogenesis medicine Phosphorylation Signal transduction Oxidative stress medicine.drug |
| Zdroj: | Biomedical Research. 38:343-350 |
| ISSN: | 1880-313X 0388-6107 |
| DOI: | 10.2220/biomedres.38.343 |
| Popis: | Iron is an essential trace metal in almost all organisms and plays an important role in the redox system. We previously reported that iron deficiency activated autophagy and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling for oxidative stress. However, regulatory mechanisms underlying the association between autophagy and Nrf2 signaling are unclear. In this study, we found that treatment of cells with an iron-specific chelator deferoxamine (DFO) increased reactive oxidative species (ROS) production by elevating the expression of p47phox and p67phox compared with that in untreated cells. The DFO treatment also induced protein aggregation and formed aggresome, which is a cellular response to misfolded protein. In addition, DFO treatment upregulated the expression of the autophagic gene p62/SQSTM1, which in turn activated intracellular proteolysis during autophagy. DFO treatment phosphorylated p62/SQSTM1 (Thr351) to activate Nrf2. However, silencing of p62/SQSTM1 followed by DFO treatment attenuated Nrf2 activation and resulted in the accumulation of carboxyl proteins compared with DFO treatment alone. These results indicated that iron deficiency activates Nrf2 signaling by modulating p62/SQSTM1 during autophagy. |
| Databáze: | OpenAIRE |
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