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Decreased SIRT1 Impairs HIF-1α Nuclear Translocation in Alveolar Epithelial Cells: A Potential Mechanism of Emphysema Progression
https://dmu.repo.nii.ac.jp/records/2000348
https://dmu.repo.nii.ac.jp/records/20003483a3aed8d-a52f-4303-9acd-4e1b2ee7302d
| 名前 / ファイル | ライセンス | アクション |
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DKMJ-3-2-1.pdf (288 KB)
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DKMJ-3-2-1-Suppl.pdf (276 KB)
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| Item type | 学術雑誌論文 / Journal Article(1) | |||||||||||||||
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| タイトル | ||||||||||||||||
| タイトル | Decreased SIRT1 Impairs HIF-1α Nuclear Translocation in Alveolar Epithelial Cells: A Potential Mechanism of Emphysema Progression | |||||||||||||||
| 言語 | en | |||||||||||||||
| 言語 | ||||||||||||||||
| 言語 | eng | |||||||||||||||
| キーワード | ||||||||||||||||
| 言語 | en | |||||||||||||||
| 主題Scheme | Other | |||||||||||||||
| 主題 | Emphysema | |||||||||||||||
| キーワード | ||||||||||||||||
| 言語 | en | |||||||||||||||
| 主題Scheme | Other | |||||||||||||||
| 主題 | HIF-1α | |||||||||||||||
| キーワード | ||||||||||||||||
| 言語 | en | |||||||||||||||
| 主題Scheme | Other | |||||||||||||||
| 主題 | Hypoxia | |||||||||||||||
| キーワード | ||||||||||||||||
| 言語 | en | |||||||||||||||
| 主題Scheme | Other | |||||||||||||||
| 主題 | SIRT1 | |||||||||||||||
| キーワード | ||||||||||||||||
| 言語 | en | |||||||||||||||
| 主題Scheme | Other | |||||||||||||||
| 主題 | VEGF | |||||||||||||||
| 資源タイプ | ||||||||||||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||||||||||||
| 資源タイプ | journal article | |||||||||||||||
| アクセス権 | ||||||||||||||||
| アクセス権 | open access | |||||||||||||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||||||||||||
| 著者 |
To, Masako
× To, Masako
× Arimoto, Yoshihito
× Honda, Natsue
× Ito, Kazuhiro
× Haruki, Kosuke
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| 書誌情報 |
en : Dokkyo Medical Journal 巻 3, 号 2, p. 77-87, 発行日 2024-06-25 |
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| 記事種別 | ||||||||||||||||
| Original | ||||||||||||||||
| 内容記述 | ||||||||||||||||
| 内容記述タイプ | Abstract | |||||||||||||||
| 内容記述 | Hypoxia-inducible factor 1 (HIF-1) is a crucial protein involved in cellular adaptation to low oxygen levels. We previously demonstrated impaired HIF-1α nuclear translocations cause impaired cellular adaptation to hypoxia in chronic obstructive pulmonary disease (COPD). However, the mechanism of impaired nuclear translocations of HIF-1α in COPD was not fully elucidated. We hypothesised that sirtuin (SIRT) 1, which is known to be decreased in the lungs of COPD patients, is involved in HIF-1α nuclear translocation. The objective of this study was to investigate the precise functions of sirtuin SIRT1 in relation to HIF-1α stabilization, nuclear translocation, and the subsequent modulation of vascular endothelial growth factor (VEGF) expression. SIRT1 was knocked down by transfection with siRNA of SIRT1 to A549 cells, and the cells were cultured under hypoxic conditions (1% O2, 5% CO2, and 94% N2). HIF-1α proteins in nuclei and whole cell extracts were measured by SDS/PAGE Western blotting, and mRNA levels of HIF-1α, VEGF, and MMP (Matrix metalloproteinase) -9 were quantified by quantitative real-time PCR. SIRT1 knockdown significantly decreased HIF-1α protein in nuclei under hypoxia without affecting the amount of HIF-1α mRNA or HIF-1α proteins in whole cells compared to control knockdown cells. Hypoxia- induced VEGF expression was suppressed by SIRT1 knockdown. Conversely, SIRT1 knockdown resulted in a further increase in MMP-9 transcription under hypoxic conditions. In conclusion, the reduction of SIRT1 leads to impaired nuclear translocation of HIF-1α under hypoxia, subsequently decreasing VEGF expression, and promoting increased MMP-9 expression under hypoxic conditions. These mechanisms may potentially contribute to the progression of emphysema. |
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| 言語 | en | |||||||||||||||
| 出版者 | ||||||||||||||||
| 出版者 | Dokkyo Medical Society | |||||||||||||||
| ISSN | ||||||||||||||||
| 収録物識別子タイプ | EISSN | |||||||||||||||
| 収録物識別子 | 2436-522X | |||||||||||||||
| 書誌レコードID | ||||||||||||||||
| 収録物識別子タイプ | NCID | |||||||||||||||
| 収録物識別子 | AA12941861 | |||||||||||||||
| 出版タイプ | ||||||||||||||||
| 出版タイプ | VoR | |||||||||||||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||||||||||
| 他の資源との関係 | ||||||||||||||||
| 関連タイプ | isIdenticalTo | |||||||||||||||
| 識別子タイプ | DOI | |||||||||||||||
| 関連識別子 | https://doi.org/10.51040/dkmj.2023-033 | |||||||||||||||
