Corrigendum: eIF3a Regulation of NHEJ Repair Protein Synthesis and Cellular Response to Ionizing Radiation

Translation initiation in protein synthesis regulated by eukaryotic initiation factors (eIFs) is a crucial step in controlling gene expression. eIF3a has been shown to regulate protein synthesis and cellular response to treatments by anticancer agents including cisplatin by regulating nucleotide excision repair. In this study, we tested the hypothesis that eIF3a regulates the synthesis of proteins important for the repair of double-strand DNA breaks induced by ionizing radiation (IR). We found that eIF3a upregulation sensitized cellular response to IR while its downregulation caused resistance to IR. eIF3a increases IR-induced DNA damages and decreases non-homologous end joining (NHEJ) activity by suppressing the synthesis of NHEJ repair proteins. Furthermore, analysis of existing patient database shows that eIF3a expression associates with better overall survival of breast, gastric, lung, and ovarian cancer patients. These findings together suggest that eIF3a plays an important role in cellular response to DNA-damaging treatments by regulating the synthesis of DNA repair proteins and, thus, eIIF3a likely contributes to the outcome of cancer patients treated with DNA-damaging strategies including IR.

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Study of the radiomodifier effect of Pityrocarpa moniliformis extract

Brazilian Journal of Radiation Sciences ◽

10.15392/bjrs.v7i2a.760 ◽

2019 ◽

Vol 7 (2A) ◽

Author(s):

João Victor Torres de Moraes ◽

Ricardo Luiz Calazans Luna Filho ◽

Williams Nascimento de Siqueira ◽

Hianna Arely Milca Fagundes Silva ◽

Dewson Rocha Pereira ◽

...

Keyword(s):

Ionizing Radiation ◽

Cellular Response ◽

Biomphalaria Glabrata ◽

Toxicity Tests ◽

Antioxidant Compounds ◽

Blastula Stage ◽

Natural Substances ◽

60Co Source ◽

60Co Gamma ◽

60Co Gamma Radiation

Ionizing radiation has been applied in several areas of knowledge, among them the study of the radiomodifier activity of natural substances. These substances can modify the cellular response to the damage induced by the radiation. Therefore, this work aimed to evaluate the radiomodifier action of Pityrocarpa moniliformis extract on Biomphalaria glabrata embryos exposed to 60Co gamma radiation. Initially, toxicity tests were performed on the extract against the B. glabrata embryos for the choice of concentration that did not cause death and embryonic malformation. Then, the antioxidant activity of the P. moniliformis extract with flavonoids and phenolic compounds was evaluated by means of the ABTS method. To evaluate the radiomodifier activity of the extract, embryos were selected in the blastula stage and irradiated with 7.5 Gy in a 60Co source (gammacell-Co60). Then, the embryos were exposed for 24 h to the extract of P. moniliformis at a concentration of 250 μg/mL. The results showed that the extract of P. moniliformis presents flavonoids and enzymatic inhibition by ABTS, which demonstrates the presence of antioxidant compounds. However, the tests of the radiomodifier activity did not present radioprotective effect for embryos exposed to ionizing radiation.

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Ionizing Radiation and Translation Control: A Link to Radiation Hormesis?

International Journal of Molecular Sciences ◽

10.3390/ijms21186650 ◽

2020 ◽

Vol 21 (18) ◽

pp. 6650

Author(s):

Usha Kabilan ◽

Tyson E. Graber ◽

Tommy Alain ◽

Dmitry Klokov

Keyword(s):

Protein Synthesis ◽

Ionizing Radiation ◽

Molecular Mechanisms ◽

Low Dose ◽

Mrna Translation ◽

Cellular Responses ◽

Translation Control ◽

Cis Acting ◽

Radiation Hormesis ◽

Downstream Signaling

Protein synthesis, or mRNA translation, is one of the most energy-consuming functions in cells. Translation of mRNA into proteins is thus highly regulated by and integrated with upstream and downstream signaling pathways, dependent on various transacting proteins and cis-acting elements within the substrate mRNAs. Under conditions of stress, such as exposure to ionizing radiation, regulatory mechanisms reprogram protein synthesis to translate mRNAs encoding proteins that ensure proper cellular responses. Interestingly, beneficial responses to low-dose radiation exposure, known as radiation hormesis, have been described in several models, but the molecular mechanisms behind this phenomenon are largely unknown. In this review, we explore how differences in cellular responses to high- vs. low-dose ionizing radiation are realized through the modulation of molecular pathways with a particular emphasis on the regulation of mRNA translation control.

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Disruption of ATM in p53-null cells causes multiple functional abnormalities in cellular response to ionizing radiation

Oncogene ◽

10.1038/sj.onc.1203172 ◽

1999 ◽

Vol 18 (50) ◽

pp. 7002-7009 ◽

Cited By ~ 74

Author(s):

Noriaki Takao ◽

Hideaki Kato ◽

Ryoichi Mori ◽

Ciaran Morrison ◽

Eiichiro Sonada ◽

...

Keyword(s):

Ionizing Radiation ◽

Cellular Response

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Does reduced gravity alter cellular response to ionizing radiation?

Radiation and Environmental Biophysics ◽

10.1007/s00411-006-0037-4 ◽

2006 ◽

Vol 45 (1) ◽

pp. 1-8 ◽

Cited By ~ 21

Author(s):

Lorenzo Manti

Keyword(s):

Ionizing Radiation ◽

Cellular Response ◽

Reduced Gravity

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The Translationally Controlled Tumor Protein and the Cellular Response to Ionizing Radiation-Induced DNA Damage

Results and Problems in Cell Differentiation - TCTP/tpt1 - Remodeling Signaling from Stem Cell to Disease ◽

10.1007/978-3-319-67591-6_12 ◽

2017 ◽

pp. 227-253 ◽

Cited By ~ 2

Author(s):

Jie Zhang ◽

Grace Shim ◽

Sonia M. de Toledo ◽

Edouard I. Azzam

Keyword(s):

Dna Damage ◽

Ionizing Radiation ◽

Cellular Response ◽

Translationally Controlled Tumor Protein ◽

Radiation Induced

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Involvement of reactive oxygen species in ionizing radiation–induced upregulation of cell surface Toll-like receptor 2 and 4 expression in human monocytic cells

Journal of Radiation Research ◽

10.1093/jrr/rrx011 ◽

2017 ◽

Vol 58 (5) ◽

pp. 626-635 ◽

Cited By ~ 8

Author(s):

Hironori Yoshino ◽

Ikuo Kashiwakura

Keyword(s):

Reactive Oxygen Species ◽

Protein Synthesis ◽

Ionizing Radiation ◽

Cell Surface ◽

Reactive Oxygen ◽

Mitogen Activated Protein Kinase ◽

Protein Synthesis Inhibitor ◽

Oxygen Species ◽

X Ray ◽

Radiation Induced

Abstract Toll-like receptors (TLRs) are pattern recognition receptors that recognize pathogen-associated molecular patterns and are indispensable for antibacterial and antiviral immunity. Our previous report showed that ionizing radiation increases the cell surface expressions of TLR2 and TLR4 and enhances their responses to agonists in human monocytic THP1 cells. The present study investigated how ionizing radiation increases the cell surface expressions of TLR2 and TLR4 in THP1 cells. The THP1 cells treated or not treated with pharmaceutical agents such as cycloheximide and N-acetyl-L-cysteine (NAC) were exposed to X-ray irradiation, following which the expressions of TLRs and mitogen-activated protein kinase were analyzed. X-ray irradiation increased the mRNA expressions of TLR2 and TLR4, and treatment with a protein synthesis inhibitor cycloheximide abolished the radiation-induced upregulation of their cell surface expressions. These results indicate that radiation increased those receptors through de novo protein synthesis. Furthermore, treatment with an antioxidant NAC suppressed not only the radiation-induced upregulation of cell surface expressions of TLR2 and TLR4, but also the radiation-induced activation of the c-Jun N-terminal kinase (JNK) pathway. Since it has been shown that the inhibitor for JNK can suppress the radiation-induced upregulation of TLR expression, the present results suggest that ionizing radiation increased the cell surface expressions of TLR2 and TLR4 through reactive oxygen species–mediated JNK activation.

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