Dysregulation of IRP1-mediated iron metabolism causes gamma ray-specific radioresistance in leukemia cells Journal Article

   

Authors:	Haro, K. J.; Sheth, A.; Scheinberg, D. A.
Article Title:	Dysregulation of IRP1-mediated iron metabolism causes gamma ray-specific radioresistance in leukemia cells
Abstract:	Iron is required for nearly all organisms, playing important roles in oxygen transport and many enzymatic reactions. Excess iron, however, can be cytotoxic. Emerging evidence suggests that radioresistance can be achieved in lower organisms by the protection of proteins, but not DNA, immediately following ionizing radiation (IR) exposure, allowing for improved DNA repair. One potential mechanism for protein protection is controlling and limiting the amount of free iron in cells, as has been demonstrated in the extremophile Deinococcus Radiodurans, reducing the potential for oxidative damage to proteins during exposure to IR. We found that iron regulatory protein 1 (IRP1) expression was markedly reduced in human myeloid leukemia HL60 cells resistant to low linear energy transfer (LET) gamma rays, but not to high LET alpha particles. Stable knockdown of IRP1 by short-hairpin RNA (shRNA) interference in radiosensitive parental cells led to radioresistance to low LET IR, reduced intracellular Fenton chemistry, reduced protein oxidation, and more rapid DNA double-strand break (DSB) repair. The mechanism of radioresistance appeared to be related to attenuated free radical-mediated cell death. Control of intracellular iron by IRPs may be a novel radioresistance mechanism in mammalian cells. © 2012 Haro et al.
Journal Title:	PLoS ONE
Volume:	7
Issue:	11
ISSN:	1932-6203
Publisher:	Public Library of Science
Date Published:	2012-01-01
Start Page:	e48841
Language:	English
DOI:	10.1371/journal.pone.0048841
PROVIDER:	scopus
PMCID:	PMC3498264
PUBMED:	23155415
DOI/URL:	http://release-www.scopus.com/inward/record.url?eid=2-s2.0-84869123994&partnerID=40&md5=edac933c442734ed0b00c6eda4f65d12
Notes:	--- - "Export Date: 3 December 2012" - "Source: Scopus"

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