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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
著者
Oshima, Keisuke Tokushima University
Watanabe, Hiroaki Tokushima University
Hamano, Hirofumi Tokushima University
木平, 孝高 Tokushima University|Fukuyama University KAKEN研究者をさがす
Hirayama, Tasuku Gifu Pharmaceutical University
永澤, 秀子 Gifu Pharmaceutical University
資料タイプ
学術雑誌論文
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.
掲載誌名
Laboratory Investigation
ISSN
15300307
00236837
cat書誌ID
AA12189985
AA00713961
出版者
Springer Nature
97
5
開始ページ
555
終了ページ
566
発行日
2017-03-06
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.
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
著者版
部局
医学系
病院
薬学系