Ferritin and the response to oxidative stress

Iron is required for normal cell growth and proliferation. However, excess iron is potentially harmful, as it can catalyse the formation of toxic reactive oxygen species (ROS) via Fenton chemistry. For this reason, cells have evolved highly regulated mechanisms for controlling intracellular iron lev...

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Bibliographic Details
Published in:Biochemical journal 2001-07, Vol.357 (Pt 1), p.241-247
Main Authors: Orino, K, Lehman, L, Tsuji, Y, Ayaki, H, Torti, S V, Torti, F M
Format: Article
Language:English
Subjects:
Cytosol - metabolism
Doxycycline - pharmacology
Electroporation
Ferritins - chemistry
Ferritins - genetics
Gene Expression Regulation - drug effects
Gene Expression Regulation - physiology
HeLa Cells
Humans
Hydrogen Peroxide - pharmacology
Iron-Regulatory Proteins
Iron-Sulfur Proteins - genetics
Iron-Sulfur Proteins - metabolism
Kinetics
Oxidative Stress - physiology
Plasmids
Promoter Regions, Genetic - drug effects
Protein Subunits
Reactive Oxygen Species - metabolism
RNA-Binding Proteins - genetics
RNA-Binding Proteins - metabolism
Tetracycline - pharmacology
Transcription, Genetic - physiology
Transfection
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Summary:Iron is required for normal cell growth and proliferation. However, excess iron is potentially harmful, as it can catalyse the formation of toxic reactive oxygen species (ROS) via Fenton chemistry. For this reason, cells have evolved highly regulated mechanisms for controlling intracellular iron levels. Chief among these is the sequestration of iron in ferritin. Ferritin is a 24 subunit protein composed of two subunit types, termed H and L. The ferritin H subunit has a potent ferroxidase activity that catalyses the oxidation of ferrous iron, whereas ferritin L plays a role in iron nucleation and protein stability. In the present study we report that increased synthesis of both subunits of ferritin occurs in HeLa cells exposed to oxidative stress. An increase in the activity of iron responsive element binding proteins in response to oxidative stress was also observed. However, this activation was transient, allowing ferritin protein induction to subsequently proceed. To assess whether ferritin induction reduced the accumulation of ROS, and to test the relative contribution of ferritin H and L subunits in this process, we prepared stable transfectants that overexpressed either ferritin H or ferritin L cDNA under control of a tetracycline-responsive promoter. We observed that overexpression of either ferritin H or ferritin L reduced the accumulation of ROS in response to oxidant challenge.
ISSN:0264-6021
1470-8728
DOI:10.1042/0264-6021:3570241