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Genipin protects against H2O2-induced oxidative damage in retinal pigment epithelial cells by promoting Nrf2 signaling.
- Source :
-
International journal of molecular medicine [Int J Mol Med] 2019 Feb; Vol. 43 (2), pp. 936-944. Date of Electronic Publication: 2018 Dec 12. - Publication Year :
- 2019
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Abstract
- Oxidative stress serves a vital function in the pathogenesis of age‑related macular degeneration (AMD); genipin (GP) possesses antioxidative properties. The present study aimed to investigate the effects of GP on retinal pigment epithelial (RPE) cells induced by H2O2 and the underlying mechanism. ARPE‑19 cells were subjected to H2O2 treatment to induce oxidative damage. Cell viability was determined via an MTT assay. Reactive oxygen species (ROS) levels and cell apoptosis were detected by flow cytometry. Nuclear factor‑erythroid 2‑related factor‑2 (Nrf2) signaling‑associated and the expression of apoptosis‑associated factors were measured using reverse transcription‑quantitative polymerase chain reaction assay and western blotting. The results revealed that 200 µM H2O2 and 30 µM GP were determined to be the optimal concentrations for subsequent experimentation. GP reversed the inhibitory effects of H2O2 by promoting cell viability, attenuating ROS accumulation and cell apoptosis, and increased the expression of Nrf2, heme oxygenase‑1 (HO‑1) and NAD(P)H: Quinine oxidoreductase 1 (NQO1); Nrf2 silencing inhibited HO‑1 and NQO1 expression. In addition, Nrf2 silencing enhanced the effects of H2O2 by promoting ROS production and cell apoptosis. Compared with H2O2, Nrf2 silencing further decreased the expression levels of B‑cell lymphoma‑2 (Bcl‑2), but increased that of Bcl‑2‑associated X protein and cleaved‑caspase‑3. The results of the present study revealed that Nrf2 silencing attenuated the protective effects of GP on H2O2‑induced injury in ARPE‑19 cells by promoting apoptosis and oxidation. Collectively, GP attenuated oxidative damage induced by H2O2 in ARPE‑19 cells. Furthermore, the molecular mechanism may be associated with the Nrf2 signaling pathway. The findings of the present study nay provide insight into a potential therapeutic agent for the treatment of AMD.
- Subjects :
- Apoptosis drug effects
Cell Line
Cell Survival drug effects
Cytoprotection drug effects
Gene Silencing
Humans
NF-E2-Related Factor 2 genetics
Oxidation-Reduction drug effects
Reactive Oxygen Species metabolism
Epithelial Cells drug effects
Epithelial Cells metabolism
Hydrogen Peroxide pharmacology
Iridoids pharmacology
NF-E2-Related Factor 2 metabolism
Oxidative Stress drug effects
Retinal Pigment Epithelium cytology
Signal Transduction drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1791-244X
- Volume :
- 43
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- International journal of molecular medicine
- Publication Type :
- Academic Journal
- Accession number :
- 30569096
- Full Text :
- https://doi.org/10.3892/ijmm.2018.4027