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Modulation of intracellular iron levels by oxidative stress implicates a novel role for iron in signal transduction

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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.

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Acknowledgments

This work was supported by NIH grants DK056160, DK064750, ES014638 and the Milton Fund (Harvard University). R.L.R-T was a fellowship recipient of FAPESP (Brazil), and E.E.J. was supported by NIH grants T90 DK070078 and T32 ES007155.

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  1. Departments of Nutrition and Genetics and Complex Disease, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA, 02115, USA

    Suman Deb, Erin E. Johnson, Raquel L. Robalinho-Teixeira & Marianne Wessling-Resnick

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  1. Suman Deb
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  2. Erin E. Johnson
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Correspondence to Marianne Wessling-Resnick.

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Deb, S., Johnson, E.E., Robalinho-Teixeira, R.L. et al. Modulation of intracellular iron levels by oxidative stress implicates a novel role for iron in signal transduction. Biometals 22, 855–862 (2009). https://doi.org/10.1007/s10534-009-9214-7

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