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Genipin protects against H2O2-induced oxidative damage in retinal pigment epithelial cells by promoting Nrf2 signaling.
Int J Mol Med. 2019 Feb; 43(2):936-944.IJ

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.

Authors+Show Affiliations

Department of Ophthalmology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, P.R. China.Department of Ophthalmology, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.Department of Ophthalmology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, P.R. China.Department of Ophthalmology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, P.R. China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30569096

Citation

Zhao, Hailan, et al. "Genipin Protects Against H2O2-induced Oxidative Damage in Retinal Pigment Epithelial Cells By Promoting Nrf2 Signaling." International Journal of Molecular Medicine, vol. 43, no. 2, 2019, pp. 936-944.
Zhao H, Wang R, Ye M, et al. Genipin protects against H2O2-induced oxidative damage in retinal pigment epithelial cells by promoting Nrf2 signaling. Int J Mol Med. 2019;43(2):936-944.
Zhao, H., Wang, R., Ye, M., & Zhang, L. (2019). Genipin protects against H2O2-induced oxidative damage in retinal pigment epithelial cells by promoting Nrf2 signaling. International Journal of Molecular Medicine, 43(2), 936-944. https://doi.org/10.3892/ijmm.2018.4027
Zhao H, et al. Genipin Protects Against H2O2-induced Oxidative Damage in Retinal Pigment Epithelial Cells By Promoting Nrf2 Signaling. Int J Mol Med. 2019;43(2):936-944. PubMed PMID: 30569096.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genipin protects against H2O2-induced oxidative damage in retinal pigment epithelial cells by promoting Nrf2 signaling. AU - Zhao,Hailan, AU - Wang,Ruiqing, AU - Ye,Mingxia, AU - Zhang,Lan, Y1 - 2018/12/12/ PY - 2018/07/19/received PY - 2018/12/04/accepted PY - 2018/12/21/pubmed PY - 2019/5/21/medline PY - 2018/12/21/entrez SP - 936 EP - 944 JF - International journal of molecular medicine JO - Int. J. Mol. Med. VL - 43 IS - 2 N2 - 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. SN - 1791-244X UR - https://www.unboundmedicine.com/medline/citation/30569096/Genipin_protects_against_H2O2_induced_oxidative_damage_in_retinal_pigment_epithelial_cells_by_promoting_Nrf2_signaling_ L2 - http://www.spandidos-publications.com/ijmm/43/2/936 DB - PRIME DP - Unbound Medicine ER -