論文

査読有り
2016年9月

Epalrestat Upregulates Heme Oxygenase-1, Superoxide Dismutase, and Catalase in Cells of the Nervous System

BIOLOGICAL & PHARMACEUTICAL BULLETIN
  • Kaori Yama
  • ,
  • Keisuke Sato
  • ,
  • Yu Murao
  • ,
  • Ryosuke Tatsunami
  • ,
  • Yoshiko Tampo

39
9
開始ページ
1523
終了ページ
1530
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1248/bpb.b16-00332
出版者・発行元
PHARMACEUTICAL SOC JAPAN

Heme oxygenase (HO)-1 has potent antioxidant and anti-inflammatory functions. Recent studies have shown that the upregulation of HO-1 is beneficial to counteract neuroinflammation, making HO-1 a new therapeutic target for neurological diseases. We have reported that epalrestat (EPS), which is currently used for the treatment of diabetic neuropathy, increases HO-1 levels through the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) in bovine aortic endothelial cells. In this study, we tested the hypothesis that EPS upregulates HO-1 via Nrf2 activation in the component cells of the nervous system, by using rat Schwann cells and human SH-SY5Y cells. Treatment of Schwann cells with EPS at near-plasma concentration led to a dramatic increase in HO-1 levels. Nrf2 knockdown by small interfering RNA (siRNA) suppressed the EPS-induced HO-1 expression. EPS did not promote the intracellular accumulation of free ferrous ion and reactive oxygen species, by increasing ferritin via Nrf2 during HO-1 induction. Moreover, EPS stimulated the expression of superoxide dismutase 1 and catalase, which also are Nrf2 target gene products. It also markedly increased HO-1 levels in SH-SY5Y cells through the activation of Nrf2. We demonstrated for the first time that EPS upregulates HO-1, superoxide dismutase, and catalase by activating Nrf2. We suggest that EPS has the potential to prevent several neurological diseases.

Web of Science ® 被引用回数 : 10

リンク情報
DOI
https://doi.org/10.1248/bpb.b16-00332
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/27439473
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000382352500017&DestApp=WOS_CPL

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