A model of interactions between radiation-induced oxidative stress, protein and DNA damage in Deinococcus radiodurans

Shuryak, Igor; Brenner, David J.

doi:10.1016/j.jtbi.2009.08.003

Cited by 31 publications

(23 citation statements)

References 48 publications

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“…A recent mathematical model of radiogenic oxidative stress is consistent with our data and can potentially be generalized to other organisms and lower radiation doses [55]. Our studies indicate that supplementation of bacteria and human cells with mixtures of peptides, nucleosides, Mn 2+ and orthophosphate, which are enriched in DR-ultrafiltrate, is a major route to radiation resistance mediated by protein protection.…”

Section: Resultssupporting

confidence: 87%

Small-Molecule Antioxidant Proteome-Shields in Deinococcus radiodurans

et al. 2010

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For Deinococcus radiodurans and other bacteria which are extremely resistant to ionizing radiation, ultraviolet radiation, and desiccation, a mechanistic link exists between resistance, manganese accumulation, and protein protection. We show that ultrafiltered, protein-free preparations of D. radiodurans cell extracts prevent protein oxidation at massive doses of ionizing radiation. In contrast, ultrafiltrates from ionizing radiation-sensitive bacteria were not protective. The D. radiodurans ultrafiltrate was enriched in Mn, phosphate, nucleosides and bases, and peptides. When reconstituted in vitro at concentrations approximating those in the D. radiodurans cytosol, peptides interacted synergistically with Mn2+ and orthophosphate, and preserved the activity of large, multimeric enzymes exposed to 50,000 Gy, conditions which obliterated DNA. When applied ex vivo, the D. radiodurans ultrafiltrate protected Escherichia coli cells and human Jurkat T cells from extreme cellular insults caused by ionizing radiation. By establishing that Mn2+-metabolite complexes of D. radiodurans specifically protect proteins against indirect damage caused by gamma-rays delivered in vast doses, our findings provide the basis for a new approach to radioprotection and insight into how surplus Mn budgets in cells combat reactive oxygen species.

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Section: Resultssupporting

confidence: 87%

Small-Molecule Antioxidant Proteome-Shields in Deinococcus radiodurans

et al. 2010

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“…This model focuses on the relation between proteins and DNA damage in the context of radiogenic oxidative stress. In spite of a greatly simplified representation of the complex biological processes involved, the authors succeeded to use this model to simulate the effect of radiation quality and low-dose effects on D. radiodurans survival (Shuryak and Brenner 2009, 2010). The simulation of the dose–response curves ( S cfu ) was used as follows.withIn this model, D is the radiation dose (kGy), α (kGy −1 ) represents the induction of double-strand breaks (DSBs), β (dimensionless) corresponds to the capacity of the cell to repair DSBs and δ (kGy −1 ) represents the inactivation of protein activity by radiation.…”

Section: Resultsmentioning

confidence: 99%

Platinum nanoparticles: an exquisite tool to overcome radioresistance

Porcel

Remita

et al. 2017

Cancer Nano

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BackgroudSmall metallic nanoparticles are proposed as potential nanodrugs to optimize the performances of radiotherapy. This strategy, based on the enrichment of tumours with nanoparticles to amplify radiation effects in the tumour, aims at increasing the cytopathic effect in tumours while healthy tissue is preserved, an important challenge in radiotherapy. Another major cause of radiotherapy failure is the radioresistance of certain cancers. Surprisingly, the use of nanoparticles to overcome radioresistance has not, to the best of our knowledge, been extensively investigated. The mechanisms of radioresistance have been extensively studied using Deinococcus radiodurans, the most radioresistant organism ever reported, as a model.MethodsIn this work, we investigated the impact of ultra-small platinum nanoparticles (1.7 nm) on this organism, including uptake, toxicity, and effects on radiation responses.ResultsWe showed that the nanoparticles penetrate D. radiodurans cells, despite the 150 nm cell wall thickness with a minimal inhibition concentration on the order of 4.8 mg L−1. We also found that the nanoparticles amplify gamma ray radiation effects by >40%.ConclusionsFinally, this study demonstrates the capacity of metallic nanoparticles to amplify radiation in radioresistant organisms, thus opening the perspective to use nanoparticles not only to improve tumour targeting but also to overcome radioresistance.Electronic supplementary materialThe online version of this article (doi:10.1186/s12645-017-0028-y) contains supplementary material, which is available to authorized users.

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“…Radiation-induced oxidative protein damage can be started by even quite low doses of radiation and can produce an alteration of the cellular redox balance, which lasts for substantial time after exposure and may contribute to changes in cell survival, proliferation, and differentiation (Shuryak and Brenner 2009). Several damages to the peptide chain or to the side-chains of amino acid residues have been identified, and some of their mechanisms of formation has been described (Griffiths et al 2002).…”

Section: Protein Oxidationmentioning

confidence: 99%