ID | 113749 |
タイトル別表記 | Inhibitory action of iron on erythropoietin
Inhibitory action of iron on erythropoietin via oxidative stress-HIF-2α pathway
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著者 |
Oshima, Keisuke
Tokushima University
堀ノ内, 裕也
Tokushima University
Watanabe, Hiroaki
Tokushima University
Hirayama, Tasuku
Gifu Pharmaceutical University
永澤, 秀子
Gifu Pharmaceutical University
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資料タイプ |
学術雑誌論文
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抄録 | Renal anemia is a major complication in chronic kidney disease (CKD). Iron supplementation, as well as erythropoiesis-stimulating agents, are widely used for treatment of renal anemia. However, excess iron causes oxidative stress via the Fenton reaction, and iron supplementation might damage remnant renal function including erythropoietin (EPO) production in CKD. EPO gene expression was suppressed in mice following direct iron treatment. Hypoxia-inducible factor-2 alpha (HIF-2α), a positive regulator of the EPO gene, was also diminished in the kidney of mice following iron treatment. Anemia-induced increase in EPO and HIF-2α expression was also inhibited by iron-treatment. In in vitro experiments using EPO-producing HepG2 cells, iron stimulation reduced the expression of the EPO gene, as well as HIF-2α. Moreover, iron treatment augmented oxidative stress, and iron-induced reduction of EPO and HIF-2α expression was restored by tempol, an anti-oxidant compound. HIF-2α interaction with the EPO promoter was inhibited by iron treatment, and was restored by tempol. These findings suggested that iron supplementation reduced EPO gene expression via an oxidative stress-HIF-2α-dependent signaling pathway.
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掲載誌名 |
Laboratory Investigation
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ISSN | 15300307
00236837
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cat書誌ID | AA12189985
AA00713961
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出版者 | Springer Nature
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巻 | 97
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号 | 5
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開始ページ | 555
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終了ページ | 566
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発行日 | 2017-03-06
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備考 | This is the Author's Accepted Manuscript of the following article: Iron suppresses erythropoietin expression via oxidative stress-dependent hypoxia-inducible factor-2 alpha inactivation, Keisuke Oshima, Yasumasa Ikeda, Yuya Horinouchi, Hiroaki Watanabe, Hirofumi Hamano, Yoshitaka Kihira, Seiji Kishi, Yuki Izawa-Ishizawa, Licht Miyamoto, Tasuku Hirayama, Hideko Nagasawa, Keisuke Ishizawa, Koichiro Tsuchiya & Toshiaki Tamaki, Laboratory Investigation 97, 555–566 (2017), which has been published in final form at https://doi.org/10.1038/labinvest.2017.11.
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言語 |
eng
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著者版フラグ |
著者版
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部局 |
医学系
病院
薬学系
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