title: Substance P promotes the recovery of oxidative stress-damaged retinal pigmented epithelial cells by modulating Akt/GSK-3β signaling.
abstract: Senescence of the retina causes an accumulation of reactive oxygen species (ROS). Oxidative stress associated with ROS can damage RPE cells, leading to neovascularization and severe ocular disorders, including age-related macular degeneration (AMD). Thus, the early treatment of the damage caused by oxidative stress is critical for preventing the development of ocular diseases such as AMD. In this study, we examined the role of substance P (SP) in the recovery of RPE cells damaged by oxidative stress.
  
  
  
  To induce oxidative stress, RPE cells were treated with H2O2 at various doses. Recovery from oxidative stress was studied following treatment with SP by analyzing cell viability, cell proliferation, cell apoptosis, and Akt/glycogen synthase kinase (GSK)-3β activation in RPE cells in vitro.
  
  
  
  H2O2 treatment reduced cellular viability in a dose-dependent manner. SP inhibited the reduction of cell viability due to H2O2 and caused increased cell proliferation and decreased cell apoptosis. Cell survival under oxidative stress requires the activation of Akt signaling that enables cells to resist oxidative stress-induced damage. SP treatment activated Akt/GSK-3β signaling in RPE cells, which were damaged due to oxidative stress, and the inhibition of Akt signaling in SP-treated RPE cells prevented SP-induced recovery. Pretreatment with the neurokinin 1 receptor (NK1R) antagonist reduced the recovery effect of SP on damaged RPE cells.
  
  
  
  SP can protect RPE cells from oxidant-induced cell death by activating Akt/GSK-3β signaling via NK1R. This study suggests the possibility of SP as a treatment for oxidative stress-related diseases.
authors: Department of Medicine, Graduate School, Kyung Hee University, Kyungheedae-ro, Dongdaemun-gu, Seoul, Republic of Korea.
authors: Sang-Min
authors: SM
authors: Baek
authors: Department of Ophthalmology, Kyung Hee University Hospital, Kyungheedae-ro, Dongdaemun-gu, Seoul, Republic of Korea.
authors: Seung-Young
authors: SY
authors: Yu
authors: Graduate School of Biotechnology & Department of Genetic Engineering, College of Life Science, Kyung Hee University Global Campus, Seochun-dong, Kiheung-ku, Yong In, Republic of Korea.
authors: Youngsook
authors: Y
authors: Son
authors: College of Medicine/East-West Medical Research Institute, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul, Republic of Korea.
authors: Hyun Sook
authors: HS
authors: Hong
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002460:Cell Line; D049109:Cell Proliferation / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D020287:In Situ Nick-End Labeling; D064729:Neurokinin-1 Receptor Antagonists / Q000494:pharmacology; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017382:Reactive Oxygen Species; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction; D013373:Substance P / Q000494:pharmacology*
chemical_list: D064729:Neurokinin-1 Receptor Antagonists; D016877:Oxidants; D017382:Reactive Oxygen Species; D018040:Receptors, Neurokinin-1; D013373:Substance P; D006861:Hydrogen Peroxide; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt