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論文
- タイトル
- タイトル（英）
- Epalrestat Alleviates Reactive Oxygen Species and Endoplasmic Reticulum Stress by Maintaining Glycosylation in IMS32 Schwann Cells Under Exposure to Galactosemic Conditions.
- 参照URL
- https://researchmap.jp/351K/published_papers/49861312
- 著者
- 著者（英）
- Hideji Yako,Naoko Niimi,Shizuka Takaku,Junji Yamauchi,Kazunori Sango
- 担当区分
- 概要
- 概要（英）
- Aldose reductase (AR), a rate-limiting enzyme in the polyol pathway, mediates the conversion of several substrates, including glucose and galactose. In rodents, galactosemia induced by galactose feeding has been shown to develop peripheral nerve lesions resembling diabetic peripheral neuropathy. However, the mechanisms by which AR-mediated responses elicited Schwan cell lesions under galactosemic conditions remain unresolved. To investigate this, we examined the mechanism of high-galactose-induced damage mediated by AR using AR inhibitors such as ranirestat and epalrestat. The exposure of IMS32 Schwann cells under high-galactose conditions led to galactitol accumulation, the increased production of reactive oxygen species (ROS), endoplasmic reticulum (ER) stress, impaired mitochondrial morphology and membrane potential, decreased glycolysis, and aberrant glycosylation. Under these experimental conditions, ranirestat inhibited intracellular galactitol in a dose-dependent manner, whereas epalrestat failed to inhibit it. Interestingly, even at low concentrations where epalrestat did not inhibit AR activity, it prevented increased ROS production, ER stress, decreased glycolysis, and aberrant RCA120-binding glycosylation; however, no effect of ranirestat on the glycosylation was observed. Epalrestat and ranirestat did not recover mitochondrial morphology. These findings suggest that ER stress is induced by aberrant glycosylation under galactosemic conditions and that epalrestat may be effective in maintaining proper glycosylation in Schwann cells in these conditions.
- 出版者・発行元
- 出版者・発行元（英）
- 誌名
- 誌名（英）
- International journal of molecular sciences
- 巻
- 26
- 号
- 4
- 開始ページ
- 終了ページ
- 出版年月
- 2025年2月12日
- 査読の有無
- 招待の有無
- 掲載種別
- 研究論文（学術雑誌）
- ISSN
- DOI URL
- https://doi.org/10.3390/ijms26041529
- 共同研究・競争的資金等の研究課題