title: Iron chelation protects the retinal pigment epithelial cell line ARPE-19 against cell death triggered by diverse stimuli.
abstract: OBJECTIVE
  Cell death can be induced by exogenous reactive oxygen species (ROS). Endogenous ROS can also play a role in cell death triggered by agents that are not themselves ROS. One of the most potent ROS-generating systems is the iron-catalyzed Fenton reaction. Herein, the authors tested whether iron plays an important role in cell death induced by diverse stimuli in retinal pigment epithelial (RPE) cells.
  
  
  METHODS
  The ability of the iron chelator salicylaldehyde isonicotinoyl hydrazone (SIH) to chelate intracellular labile iron was tested in the human cell line ARPE-19. The ability of SIH to protect against RPE cell death induced by hydrogen peroxide, staurosporine, anti-Fas, and exposure to A2E plus blue light was determined. ROS production by staurosporine was assessed in the presence and absence of SIH. The protective activity of SIH was compared with that of other iron chelators and an antioxidant.
  
  
  RESULTS
  Acute exposure to SIH was nontoxic and at least partially protective against cell death induced by all tested agents. On a molar basis, SIH was more protective against hydrogen peroxide than other iron chelators and an antioxidant. SIH decreased levels of staurosporine-induced ROS.
  
  
  CONCLUSIONS
  Iron chelation with SIH can decrease levels of ROS and protect RPE cells against cell death induced by diverse stimuli. These results suggest a central role for iron in cell death pathways, potentially involving the generation of oxidative stress. SIH or related iron chelators may prove useful for protection against diseases involving RPE death, such as AMD.
authors.affiliation: F. M. Kirby Center for Molecular Ophthalmology and the.
authors.forename: Nina
authors.initials: N
authors.lastname: Lukinova
authors.forename: Jared
authors.initials: J
authors.lastname: Iacovelli
authors.forename: Tzvete
authors.initials: T
authors.lastname: Dentchev
authors.forename: Natalie
authors.initials: N
authors.lastname: Wolkow
authors.forename: Allan
authors.initials: A
authors.lastname: Hunter
authors.forename: Defne
authors.initials: D
authors.lastname: Amado
authors.forename: Gui-Shuang
authors.initials: GS
authors.lastname: Ying
authors.forename: Janet R
authors.initials: JR
authors.lastname: Sparrow
authors.forename: Joshua L
authors.initials: JL
authors.lastname: Dunaief
mesh_terms: D000447:Aldehydes / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000633:toxicity; D058846:Antibodies, Monoclonal, Murine-Derived; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D006835:Hydrazones / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000633:toxicity; D007501:Iron; D007502:Iron Chelating Agents / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D011726:Pyridinium Compounds / Q000633:toxicity; D017382:Reactive Oxygen Species / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D012176:Retinoids / Q000633:toxicity; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019311:Staurosporine / Q000633:toxicity
chemical_list: C112040:A2-E (N-retinylidene-N-retinylethanolamine); D000447:Aldehydes; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; C045076:Fenton's reagent; D006835:Hydrazones; D007502:Iron Chelating Agents; D011726:Pyridinium Compounds; D017382:Reactive Oxygen Species; D012176:Retinoids; C411023:anti-Fas monoclonal antibody; C413684:salicylaldehyde isonicotinoyl hydrazone; D006861:Hydrogen Peroxide; D007501:Iron; D007770:L-Lactate Dehydrogenase; D019311:Staurosporine