title: Modulation of intracellular iron levels by oxidative stress implicates a novel role for iron in signal transduction.
abstract: Reactive oxygen species (ROS) display cytotoxicity that can be exacerbated by iron. Paradoxically, HeLa cells treated with the ROS-generators menadione and 2,3-dimethoxy-1,4-naphthoquinone display increased free labile iron. HeLa cells exposed to ROS undergo apoptosis but iron chelation limits the extent of cell death suggesting the rise in intracellular iron plays a signaling role in this pathway. This idea is supported by the fact that iron chelation also alters the pattern of ROS-induced phosphorylation of stress-activated protein kinases SAPK/JNK and p38 MAPK. Thus, ROS-induced increases in cellular free iron contribute to signaling events triggered during oxidative stress response.
authors.affiliation: Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: Suman
authors.initials: S
authors.lastname: Deb
authors.forename: Erin E
authors.initials: EE
authors.lastname: Johnson
authors.forename: Raquel L
authors.initials: RL
authors.lastname: Robalinho-Teixeira
authors.forename: Marianne
authors.initials: M
authors.lastname: Wessling-Resnick
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D006367:HeLa Cells; D006801:Humans; D007501:Iron / Q000378:metabolism*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D009285:Naphthoquinones / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000502:physiology*; D024483:Vitamin K 3 / Q000494:pharmacology; D014815:Vitamins / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D009285:Naphthoquinones; D014815:Vitamins; C063002:2,3-dimethoxy-1,4-naphthoquinone; D024483:Vitamin K 3; D007501:Iron; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4