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

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

Content Provider	Semantic Scholar
Author	Yama, Kaori Sato, Keisuke Murao, Yu Tatsunami, Ryosuke Tampo, Yoshiko
Copyright Year	2016
Abstract	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.
File Format	PDF HTM / HTML
DOI	10.1248/bpb.b16-00332
PubMed reference number	27439473
Journal	Medline
Volume Number	39
Issue Number	9
Alternate Webpage(s)	https://www.jstage.jst.go.jp/article/bpb/39/9/39_b16-00332/_pdf/-char/en
Alternate Webpage(s)	https://doi.org/10.1248/bpb.b16-00332
Journal	Biological & pharmaceutical bulletin
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article

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