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Exendin-4 Protects Human Retinal Pigment Epithelial Cells from H2O2-Induced Oxidative Damage via Activation of NRF2 Signaling.
Ophthalmic Res. 2020; 63(4):404-412.OR

Abstract

AIMS

Oxidative damage plays a vital role in the pathogenesis of age-related macular degeneration (AMD). Exendin-4 (EX4), a glucagon-like peptide-1 receptor agonist, possesses several pharmacological functions, such as anti-inflammatory and antioxidative properties. However, the effects and mechanism of EX4 on oxidative stress in retinal pigment epithelial (RPE) cells induced by hydrogen peroxide (H2O2) remain unclear. The present study aimed to investigate the protective mechanism of EX4 on human RPE cells subjected to oxidative stress.

METHODS

Human RPE ARPE-19 cells were treated with H2O2 to induce oxidative damage. Cell viability was determined by Cell Counting Kit-8 and lactate dehydrogenase assay. Levels of intracellular reactive oxygen species (ROS), malonyldialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH) were measured using commercial kits. The expression of nuclear factor erythroid 2-related factor-2 (NRF2), heme oxygenase-1 (HO-1), and NAD(P)H:quinone oxidoreductase-1 (NQO-1) was measured using reverse transcription quantitative polymerase chain reaction assay and western blot, respectively.

RESULTS

H2O2 significantly induced oxidative stress to reduce viability of RPE cells and increased intracellular ROS generation. EX4 significantly ameliorated H2O2-induced oxidative damage by reducing intracellular ROS generation, decreasing MDA concentration, and increasing antioxidant enzymes activities (SOD and GSH). In addition, EX4 markedly increased expression of NRF2, HO-1, and NQO-1 and significantly improved protein expression of NRF2 and HO-1 in H2O2-treated ARPE-19 cells, caused by increased nuclear NRF2 protein expression. NRF2 knockdown by targeted siRNA alleviated EX4-mediated HO-1 expression and significantly nullified EX4-mediated RPE cell protection against H2O2.

CONCLUSIONS

EX4 attenuated oxidative damage induced by H2O2 in ARPE-19 cells through the activation of the NRF2 signaling pathway. The findings suggested that EX4 may be a potential therapeutic agent for the treatment of AMD.

Authors+Show Affiliations

Department of Ophthalmology, Affiliated Hospital of Yanbian University, Yanji, China.Department of Ophthalmology, Affiliated Hospital of Yanbian University, Yanji, China.Department of Ophthalmology, Affiliated Hospital of Yanbian University, Yanji, China.Department of Nephrology, Affiliated Hospital of Yanbian University, Yanji, China. Postdoctoral Research Station, Affiliated Hospital of Yanbian University, Yanji, China.Department of Ophthalmology, Affiliated Hospital of Yanbian University, Yanji, China, 13009082375@163.com. Postdoctoral Research Station, Affiliated Hospital of Yanbian University, Yanji, China, 13009082375@163.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31865348

Citation

Cui, Renzhe, et al. "Exendin-4 Protects Human Retinal Pigment Epithelial Cells From H2O2-Induced Oxidative Damage Via Activation of NRF2 Signaling." Ophthalmic Research, vol. 63, no. 4, 2020, pp. 404-412.
Cui R, Tian L, Lu D, et al. Exendin-4 Protects Human Retinal Pigment Epithelial Cells from H2O2-Induced Oxidative Damage via Activation of NRF2 Signaling. Ophthalmic Res. 2020;63(4):404-412.
Cui, R., Tian, L., Lu, D., Li, H., & Cui, J. (2020). Exendin-4 Protects Human Retinal Pigment Epithelial Cells from H2O2-Induced Oxidative Damage via Activation of NRF2 Signaling. Ophthalmic Research, 63(4), 404-412. https://doi.org/10.1159/000504891
Cui R, et al. Exendin-4 Protects Human Retinal Pigment Epithelial Cells From H2O2-Induced Oxidative Damage Via Activation of NRF2 Signaling. Ophthalmic Res. 2020;63(4):404-412. PubMed PMID: 31865348.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Exendin-4 Protects Human Retinal Pigment Epithelial Cells from H2O2-Induced Oxidative Damage via Activation of NRF2 Signaling. AU - Cui,Renzhe, AU - Tian,Lianji, AU - Lu,Di, AU - Li,Huiying, AU - Cui,Jun, Y1 - 2019/12/20/ PY - 2019/07/04/received PY - 2019/11/18/accepted PY - 2019/12/23/pubmed PY - 2021/6/5/medline PY - 2019/12/23/entrez KW - Age-related macular degeneration KW - Exendin-4 KW - Nuclear factor erythroid 2-related factor-2 KW - Oxidative damage KW - Retinal pigment epithelial cell SP - 404 EP - 412 JF - Ophthalmic research JO - Ophthalmic Res VL - 63 IS - 4 N2 - AIMS: Oxidative damage plays a vital role in the pathogenesis of age-related macular degeneration (AMD). Exendin-4 (EX4), a glucagon-like peptide-1 receptor agonist, possesses several pharmacological functions, such as anti-inflammatory and antioxidative properties. However, the effects and mechanism of EX4 on oxidative stress in retinal pigment epithelial (RPE) cells induced by hydrogen peroxide (H2O2) remain unclear. The present study aimed to investigate the protective mechanism of EX4 on human RPE cells subjected to oxidative stress. METHODS: Human RPE ARPE-19 cells were treated with H2O2 to induce oxidative damage. Cell viability was determined by Cell Counting Kit-8 and lactate dehydrogenase assay. Levels of intracellular reactive oxygen species (ROS), malonyldialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH) were measured using commercial kits. The expression of nuclear factor erythroid 2-related factor-2 (NRF2), heme oxygenase-1 (HO-1), and NAD(P)H:quinone oxidoreductase-1 (NQO-1) was measured using reverse transcription quantitative polymerase chain reaction assay and western blot, respectively. RESULTS: H2O2 significantly induced oxidative stress to reduce viability of RPE cells and increased intracellular ROS generation. EX4 significantly ameliorated H2O2-induced oxidative damage by reducing intracellular ROS generation, decreasing MDA concentration, and increasing antioxidant enzymes activities (SOD and GSH). In addition, EX4 markedly increased expression of NRF2, HO-1, and NQO-1 and significantly improved protein expression of NRF2 and HO-1 in H2O2-treated ARPE-19 cells, caused by increased nuclear NRF2 protein expression. NRF2 knockdown by targeted siRNA alleviated EX4-mediated HO-1 expression and significantly nullified EX4-mediated RPE cell protection against H2O2. CONCLUSIONS: EX4 attenuated oxidative damage induced by H2O2 in ARPE-19 cells through the activation of the NRF2 signaling pathway. The findings suggested that EX4 may be a potential therapeutic agent for the treatment of AMD. SN - 1423-0259 UR - https://www.unboundmedicine.com/medline/citation/31865348/Exendin_4_Protects_Human_Retinal_Pigment_Epithelial_Cells_from_H2O2_Induced_Oxidative_Damage_via_Activation_of_NRF2_Signaling_ L2 - https://www.karger.com?DOI=10.1159/000504891 DB - PRIME DP - Unbound Medicine ER -