Modulation of intracellular iron levels by oxidative stress implicates a novel role for iron in signal transduction.
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.
Deb
Suman
S
Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA.
Johnson
Erin E
EE
Robalinho-Teixeira
Raquel L
RL
Wessling-Resnick
Marianne
M
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
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