title: Inhibition of the oxidative stress-induced miR-23a protects the human retinal pigment epithelium (RPE) cells from apoptosis through the upregulation of glutaminase and glutamine uptake.
abstract: The degeneration of retinal pigment epithelium (RPE) cells in the sub retinal pigment epithelial space and choroid is an initial pathological characteristic for the age-related macular degeneration which is the leading cause of severe vision loss in old people. Moreover, oxidative stress is implicated as a major inducer of RPE cell death. Here, we assessed the correlation between the H2O2-induced RPE cell death and glutamine metabolism. We found under low glutamine supply (20 %), the ARPE-19 cells were more susceptive to H2O2-induced apoptosis. Moreover, the glutamine uptake and the glutaminase (GLS) were suppressed by H2O2 treatments. Moreover, we observed miR-23a was upregulated by H2O2 treatments and overexpression of miR-23a significantly sensitized ARPE-19 cells to H2O2. Importantly, Western blotting and luciferase assay demonstrated GLS1 is a direct target of miR-23a in RPE cells. Inhibition of the H2O2-induced miR-23a by antagomiR protected the RPE cells from the oxidative stress-induced cell death. In addition, recovery of GLS1 expression in miR-23a overexpressed RPE cells rescued the H2O2-induced cell death. This study illustrated a mechanism for the protection of the oxidative-induced RPE cell death through the recovery of glutamine metabolism by inhibition of miR-23a, contributing to the discovery of novel targets and the developments of therapeutic strategies for the prevention of RPE cells from oxidative stress.
authors.affiliation: Department of Ophthalmology, Daqing Oilfield General Hospital, No. 9 Zhongkang Street, Saertu District, Daqing, 163000, Heilongjiang, China. li_dandan_2015@163.com.
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, Daqing Oilfield General Hospital, No. 9 Zhongkang Street, Saertu District, Daqing, 163000, Heilongjiang, China.
authors.forename: Bin-Wu
authors.initials: BW
authors.lastname: Zhong
authors.affiliation: Department of Ophthalmology, Daqing Oilfield General Hospital, No. 9 Zhongkang Street, Saertu District, Daqing, 163000, Heilongjiang, China.
authors.forename: Hai-Xia
authors.initials: HX
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology, Daqing Oilfield General Hospital, No. 9 Zhongkang Street, Saertu District, Daqing, 163000, Heilongjiang, China.
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Zhou
authors.affiliation: Department of Ophthalmology, Daqing Oilfield General Hospital, No. 9 Zhongkang Street, Saertu District, Daqing, 163000, Heilongjiang, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Ophthalmology, Daqing Oilfield General Hospital, No. 9 Zhongkang Street, Saertu District, Daqing, 163000, Heilongjiang, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Ophthalmology, Daqing Oilfield General Hospital, No. 9 Zhongkang Street, Saertu District, Daqing, 163000, Heilongjiang, China.
authors.forename: Gui-Chun
authors.initials: GC
authors.lastname: Xu
authors.affiliation: Department of Ophthalmology, Daqing Oilfield General Hospital, No. 9 Zhongkang Street, Saertu District, Daqing, 163000, Heilongjiang, China.
authors.forename: Chun-Sheng
authors.initials: CS
authors.lastname: Luan
authors.affiliation: Department of Ophthalmology, Daqing Oilfield General Hospital, No. 9 Zhongkang Street, Saertu District, Daqing, 163000, Heilongjiang, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Fang
mesh_terms: D017209:Apoptosis; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D005972:Glutaminase / Q000235:genetics / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D035683:MicroRNAs / Q000235:genetics*; D018384:Oxidative Stress; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C552430:MIRN23a microRNA, human; D035683:MicroRNAs; D005973:Glutamine; D006861:Hydrogen Peroxide; C579480:GLS protein, human; D005972:Glutaminase
keywords: Apoptosis; Glutaminase; Glutamine; The human retinal pigment epithelium cells; The oxidative stress-induced miR-23a