論文 - 詳細
| RRC ID | 60799 |
|---|---|
| 著者 | Ito F, Yanatori I, Maeda Y, Nimura K, Ito S, Hirayama T, Nagasawa H, Kohyama N, Okazaki Y, Akatsuka S, Toyokuni S. |
| タイトル | Asbestos conceives Fe(II)-dependent mutagenic stromal milieu through ceaseless macrophage ferroptosis and β-catenin induction in mesothelium. |
| ジャーナル | Redox Biol |
| Abstract |
Asbestos is still a social burden worldwide as a carcinogen causing malignant mesothelioma. Whereas recent studies suggest that local iron reduction is a preventive strategy against carcinogenesis, little is known regarding the cellular and molecular mechanisms surrounding excess iron. Here by differentially using high-risk and low-risk asbestos fibers (crocidolite and anthophyllite, respectively), we identified asbestos-induced mutagenic milieu for mesothelial cells. Rat and cell experiments revealed that phagocytosis of asbestos by macrophages results in their distinctive necrotic death; initially lysosome-depenent cell death and later ferroptosis, which increase intra- and extra-cellular catalytic Fe(II). DNA damage in mesothelial cells, as assessed by 8-hydroxy-2'-deoxyguanosine and γ-H2AX, increased after crocidolite exposure during regeneration accompanied by β-catenin activation. Conversely, β-catenin overexpression in mesothelial cells induced higher intracellular catalytic Fe(II) with increased G2/M cell-cycle fraction, when p16INK4A genomic loci localized more peripherally in the nucleus. Mesothelial cells after challenge of H2O2 under β-catenin overexpression presented low p16INK4A expression with a high incidence of deletion in p16INK4A locus. Thus, crocidolite generated catalytic Fe(II)-rich mutagenic environment for mesothelial cells by necrotizing macrophages with lysosomal cell death and ferroptosis. These results suggest novel molecular strategies to prevent mesothelial carcinogenesis after asbestos exposure. |
| 巻・号 | 36 |
| ページ | 101616 |
| 公開日 | 2020-9-1 |
| DOI | 10.1016/j.redox.2020.101616 |
| PII | S2213-2317(20)30821-1 |
| PMID | 32863225 |
| PMC | PMC7330611 |
| MeSH | Animals Asbestos* Epithelium Ferroptosis* Ferrous Compounds Hydrogen Peroxide Macrophages Mesothelioma* Mutagens Rats beta Catenin / genetics |
| IF | 9.986 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 遺伝子材料 | pCMV-VSV-G-RSV-Rev (RDB04393) pCAG-HIVgp (RDB04394) |
| ヒト・動物細胞 | 293T(RCB2202) RAW 264(RCB0535) THP-1(RCB1189) |