title: Ginsenoside Rg-1 protects retinal pigment epithelium (RPE) cells from cobalt chloride (CoCl2) and hypoxia assaults.
abstract: Severe retinal ischemia causes persistent visual impairments in eye diseases. Retinal pigment epithelium (RPE) cells are located near the choroidal capillaries, and are easily affected by ischemic or hypoxia. Ginsenoside Rg-1 has shown significant neuroprotective effects. This study was performed to test the cytoprotective effect of ginsenoside Rg-1 in RPE cells against hypoxia and cobalt chloride (CoCl2) assaults, and to understand the underlying mechanisms. We found that Rg-1 pre-administration significantly inhibited CoCl2- and hypoxia-induced RPE cell death and apoptosis. Reactive oxygen specisis (ROS)-dependent p38 and c-Jun NH(2)-terminal kinases (JNK) MAPK activation was required for CoCl2-induced RPE cell death, and Rg-1 pre-treatment significantly inhibited ROS production and following p38/JNK activation. Further, CoCl2 suppressed pro-survival mTOR complex 1 (mTORC1) activation in RPE cells through activating of AMP-activated protein kinase (AMPK), while Rg-1 restored mTORC1 activity through inhibiting AMPK activation. CoCl2-induced AMPK activation was also dependent on ROS production, and anti-oxidant N-acetylcysteine (NAC) prevented AMPK activation and RPE cell death by CoCl2. Our results indicated that Rg-1 could be further investigated as a novel cell-protective agent for retinal ischemia.
authors.affiliation: Department of Eye, the Affiliated Eye Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Ke-Ran
authors.initials: KR
authors.lastname: Li
authors.affiliation: Institute of Neuroscience, Soochow University, Suzhou, Jiangsu, China.
authors.forename: Zhi-Qing
authors.initials: ZQ
authors.lastname: Zhang
authors.affiliation: Department of Eye, the Affiliated Eye Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Yao
authors.affiliation: Department of Eye, the Affiliated Eye Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Yu-Xia
authors.initials: YX
authors.lastname: Zhao
authors.affiliation: The Center for Safety Evaluation of Drugs, Academic Institute of Pharmaceutical Science, China Pharmaceutical University, Nanjing, Jiangsu, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Duan
authors.affiliation: Institute of Neuroscience, Soochow University, Suzhou, Jiangsu, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Cao
authors.affiliation: Department of Eye, the Affiliated Eye Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Jiang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015687:Cell Hypoxia / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003035:Cobalt / Q000633:toxicity*; D019610:Cytoprotection / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D036145:Ginsenosides / Q000494:pharmacology*; D006801:Humans; D000076222:Mechanistic Target of Rapamycin Complex 1; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D046912:Multiprotein Complexes / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000166:cytology* / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D036145:Ginsenosides; D046912:Multiprotein Complexes; D017382:Reactive Oxygen Species; D003035:Cobalt; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D020928:Mitogen-Activated Protein Kinases; C018021:cobaltous chloride; C035054:ginsenoside Rg1