論文 - 詳細
| RRC ID | 54900 |
|---|---|
| 著者 | Buck T, Hack CT, Berg D, Berg U, Kunz L, Mayerhofer A. |
| タイトル | The NADPH oxidase 4 is a major source of hydrogen peroxide in human granulosa-lutein and granulosa tumor cells. |
| ジャーナル | Sci Rep |
| Abstract |
H2O2 is a reactive oxygen species (ROS), which can diffuse away from its site of generation and may act as a cell-to-cell signaling factor. The mechanisms responsible for the generation of H2O2 in human ovarian follicles and possible signaling role(s) of H2O2 are not well known. We identified a source of H2O2, the enzyme NADPH oxidase (NOX) 4, in isolated differentiated, in-vitro fertilisation-derived human granulosa-lutein cells (GCs), in proliferating human granulosa tumour cells (KGN), as well as in situ in cells of growing ovarian follicles. H2O2 was readily detected in the supernatant of cultured GCs and KGN cells. H2O2 levels were significantly lowered by the NOX4 blocker GKT137831, indicating a pronounced contribution of NOX4 to overall H2O2 generation by these cells. We provide evidence that extracellular H2O2 is taken up by GCs, which is facilitated by aquaporins (peroxiporins). We thus conclude that GC-derived H2O2 might act as autocrine/paracrine factor. Addition of H2O2 increased MAPK-phosphorylation in GCs. Moreover, reducing H2O2 production with GKT137831 slowed proliferation of KGN cells. Our results pinpoint NOX4 and H2O2 as physiological players in the regulation of GC functions. |
| 巻・号 | 9(1) |
| ページ | 3585 |
| 公開日 | 2019-3-5 |
| DOI | 10.1038/s41598-019-40329-8 |
| PII | 10.1038/s41598-019-40329-8 |
| PMID | 30837663 |
| PMC | PMC6400953 |
| MeSH | Adolescent Adult Cell Proliferation Cells, Cultured Female Granulosa Cell Tumor / metabolism* Granulosa Cell Tumor / pathology Granulosa Cells / cytology Granulosa Cells / metabolism* Humans Hydrogen Peroxide / metabolism* Lutein / metabolism* NADPH Oxidase 4 / genetics NADPH Oxidase 4 / metabolism* Phosphorylation Reactive Oxygen Species / metabolism Signal Transduction Young Adult |
| IF | 4.011 |
| 引用数 | 6 |
| 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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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 2 |
| 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 | |
| ヒト・動物細胞 | KGN(RCB1154) |