1. The Protective Effect of Hispidin against Hydrogen Peroxide-Induced Oxidative Stress in ARPE-19 Cells via Nrf2 Signaling Pathway
- Author
-
Siu-Fung Chau, Sung-Ying Huang, Shu-Fang Chang, and Sheng-Chun Chiu
- Subjects
0301 basic medicine ,Adult ,Cell Survival ,NF-E2-Related Factor 2 ,lcsh:QR1-502 ,hydrogen peroxide ,Retinal Pigment Epithelium ,medicine.disease_cause ,Protective Agents ,Biochemistry ,lcsh:Microbiology ,Article ,Nrf2 ,Cell Line ,03 medical and health sciences ,chemistry.chemical_compound ,Structure-Activity Relationship ,0302 clinical medicine ,hispidin ,medicine ,Humans ,oxidative stress ,Molecular Biology ,age-related macular degeneration ,biology ,Dose-Response Relationship, Drug ,Chemistry ,GCLM ,Transfection ,biology.organism_classification ,Cell biology ,030104 developmental biology ,GCLC ,Phellinus linteus ,Pyrones ,030220 oncology & carcinogenesis ,Hispidin ,NAD+ kinase ,ARPE-19 ,Oxidative stress ,Intracellular ,Signal Transduction - Abstract
Hispidin, a polyphenol compound isolated from Phellinus linteus, has been reported to possess antioxidant activities. In this study, we aimed to investigate the mechanisms underlying the protective effect of hispidin against hydrogen peroxide (H2O2)-induced oxidative stress on Adult Retinal Pigment Epithelial cell line-19 (ARPE-19) cells. Hispidin was not cytotoxic to ARPE-19 cells at concentrations of less than 50 &mu, M. The levels of intracellular reactive oxygen species (ROS) were analyzed by dichlorofluorescin diacetate (DCFDA) staining. Hispidin significantly restored H2O2-induced cell death and reduced the levels of intracellular ROS. The expression levels of antioxidant enzymes, such as NAD(P)H:Quinine oxidoreductase-1 (NQO-1), heme oxygenase-1 (HO-1), glutamate-cysteine ligase catalytic subunit (GCLC), and glutamate-cysteine ligase modifier subunit (GCLM) were examined using real-time PCR and Western blotting. Our results showed that hispidin markedly enhanced the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), HO-1, NQO-1, GCLM, and GCLC in a dose-dependent manner. Furthermore, knockdown experiments revealed that transfection with Nrf2 siRNA successfully suppresses the hispidin activated Nrf2 signaling in ARPE-19 cells. Moreover, activation of the c-Jun N-terminal kinase (JNK) pathway is involved in mediating the protective effects of hispidin on the ARPE-19 cells. Thus, the present study demonstrated that hispidin provides protection against H2O2-induced damage in ARPE-19 cells via activation of Nrf2 signaling and up-regulation of its downstream targets, including Phase II enzymes, which might be associated with the activation of the JNK pathway.
- Published
- 2019
- Full Text
- View/download PDF