title: Artemisinin protects human retinal pigment epithelial cells from hydrogen peroxide-induced oxidative damage through activation of ERK/CREB signaling.
abstract: The pathological increase in the levels of reactive oxygen species (ROS) in the retinal pigment epithelium (RPE), is implicated in the development of age-related macular degeneration (AMD). The discovery of drug candidates to effectively protect RPE cells from oxidative damage is required to resolve the pathological aspects and modify the process of AMD. In this study, a FDA-approved anti-malaria drug, Artemisinin was found to suppress hydrogen peroxide (H2O2)-induced cell death in human RPE cell-D407 cells. Further study showed that Artemisinin significantly suppressed H2O2-induced D407 cell death by restoring abnormal changes in nuclear morphology, intracellular ROS, mitochondrial membrane potential and apoptotic biomarkers. Western blotting analysis showed that Artemisinin was able to activate extracellular regulated ERK/CREB survival signaling. Furthermore, Artemisinin failed to suppress H2O2-induced cytotoxicity and the increase of caspase 3/7 activity in the presence of the ERK inhibitor PD98059. Taken together, these results suggest that Artemisinin is a potential protectant with the pro-survival effects against H2O2insult through activation of the ERK/CREB pathway.
authors.affiliation: Faculty of Health Science, University of Macau, Macau, China.
authors.forename: Cheong-Meng
authors.initials: CM
authors.lastname: Chong
authors.affiliation: Faculty of Health Science, University of Macau, Macau, China. Electronic address: wenhuazheng@umac.mo.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Zheng
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D037621:Artemisinins / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008268:Macular Degeneration / Q000378:metabolism / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D020011:Protective Agents / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D037621:Artemisinins; D017362:Cyclic AMP Response Element-Binding Protein; D020011:Protective Agents; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D048049:Extracellular Signal-Regulated MAP Kinases; D053148:Caspase 3; D053179:Caspase 7
keywords: Age-related macular degeneration; Artemisinin; ERK; ROS; Retinal pigment epithelial cells