title: 5-HMF prevents against oxidative injury via APE/Ref-1.
abstract: Oxidative injury is involved in many diseases, including ischemic and neurodegenerative diseases. Antioxidant drugs can be used to relieve the oxidative injury caused by these diseases; however, there are very few antioxidant drugs available for clinical use. In this study, we found that 5-(hydroxymethyl)-2-furfural (5-HMF) protects against the oxidative damage induced by cerebral ischemia in rats or by hydrogen peroxide (H2O2) in PC12 cells. We demonstrated that 5-HMF performs this function via apurinic/apyrimidinic endonuclease/redox factor-1 (APE/Ref-1). APE/Ref-1 is a multifunctional protein involved in oxidative DNA damage repair through the base excision repair (BER) pathway and in the regulation of the DNA-binding activity of several transcription factors. The current study focused on the role of APE/Ref-1 in the antioxidative properties of 5-HMF. The results show that 5-HMF inhibited the reduction of APE/Ref-1 protein level caused by cerebral ischemia-reperfusion injury in rats or H2O2 treatment in PC12 cells. Treatment with an APE/Ref-1 inhibitor blocked 5-HMF-induced protection, suggesting that APE/Ref-1's DNA repair function contributes to antioxidation. In conclusion, this study suggests that APE/Ref-1 may be a potential target for antioxidant drugs.
authors.affiliation: Department of Cognitive Science, Beijing Institute of Basic Medical Sciences , Beijing , P. R. China.
authors.forename: J-H
authors.initials: JH
authors.lastname: Zhang
authors.forename: Y
authors.initials: Y
authors.lastname: Di
authors.forename: L-Y
authors.initials: LY
authors.lastname: Wu
authors.forename: Y-L
authors.initials: YL
authors.lastname: He
authors.forename: T
authors.initials: T
authors.lastname: Zhao
authors.forename: X
authors.initials: X
authors.lastname: Huang
authors.forename: X-F
authors.initials: XF
authors.lastname: Ding
authors.forename: K-W
authors.initials: KW
authors.lastname: Wu
authors.forename: M
authors.initials: M
authors.lastname: Fan
authors.forename: L-L
authors.initials: LL
authors.lastname: Zhu
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism; D004249:DNA Damage; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005662:Furaldehyde / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D016716:PC12 Cells; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*
chemical_list: D000975:Antioxidants; C008046:5-hydroxymethylfurfural; D005662:Furaldehyde; C470319:Apex1 protein, rat; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase
keywords: 5-HMF; APE/Ref-1; DNA damage; apoptosis; brain ischemia; oxidative injury