scholarly journals The Role of the Nuclear Factor κB Pathway in the Cellular Response to Low and High Linear Energy Transfer Radiation

2018 ◽  
Vol 19 (8) ◽  
pp. 2220 ◽  
Author(s):  
Christine Hellweg ◽  
Luis Spitta ◽  
Kristina Koch ◽  
Arif Chishti ◽  
Bernd Henschenmacher ◽  
...  
Keyword(s):  
Energy Transfer ◽  
Linear Energy Transfer ◽  
Heavy Ions ◽  
Cellular Response ◽  
Radiation Risk ◽  
Nuclear Factor Κb ◽  
Radiation Response ◽  
Nuclear Factor ◽  
X Rays ◽  
Knock Down

Astronauts are exposed to considerable doses of space radiation during long-term space missions. As complete shielding of the highly energetic particles is impracticable, the cellular response to space-relevant radiation qualities has to be understood in order to develop countermeasures and to reduce radiation risk uncertainties. The transcription factor Nuclear Factor κB (NF-κB) plays a fundamental role in the immune response and in the pathogenesis of many diseases. We have previously shown that heavy ions with a linear energy transfer (LET) of 100–300 keV/µm have a nine times higher potential to activate NF-κB compared to low-LET X-rays. Here, chemical inhibitor studies using human embryonic kidney cells (HEK) showed that the DNA damage sensor Ataxia telangiectasia mutated (ATM) and the proteasome were essential for NF-κB activation in response to X-rays and heavy ions. NF-κB’s role in cellular radiation response was determined by stable knock-down of the NF-κB subunit RelA. Transfection of a RelA short-hairpin RNA plasmid resulted in higher sensitivity towards X-rays, but not towards heavy ions. Reverse Transcriptase real-time quantitative PCR (RT-qPCR) showed that after exposure to X-rays and heavy ions, NF-κB predominantly upregulates genes involved in intercellular communication processes. This process is strictly NF-κB dependent as the response is completely absent in RelA knock-down cells. NF-κB’s role in the cellular radiation response depends on the radiation quality.

scholarly journals Activation of the Nuclear Factor κB pathway by heavy ion beams of different linear energy transfer

2011 ◽  
Vol 87 (9) ◽  
pp. 954-963 ◽  
Author(s):  
Christine E. Hellweg ◽  
Christa Baumstark-Khan ◽  
Claudia Schmitz ◽  
Patrick Lau ◽  
Matthias M. Meier ◽  
...  
Keyword(s):  
Energy Transfer ◽  
Linear Energy Transfer ◽  
Nuclear Factor Κb ◽  
Heavy Ion ◽  
Ion Beams ◽  
Nuclear Factor

UV stimulation induces nuclear factor κB (NF-κB) DNA-binding activity but not transcriptional activation

2001 ◽  
Vol 29 (6) ◽  
pp. 688-691 ◽  
Author(s):  
K. J. Campbell ◽  
N. R. Chapman ◽  
N. D. Perkins
Keyword(s):  
Dna Binding ◽  
Transcriptional Activation ◽  
Cellular Response ◽  
Uv Light ◽  
Binding Protein ◽  
Nuclear Factor Κb ◽  
Camp Response Element Binding ◽  
Binding Activity ◽  
Nuclear Factor ◽  
Dna Binding Activity

The cellular response to DNA-damaging agents is partly mediated by DNA-binding transcription factors such as p53 and nuclear factor κB (NF-κB). Typically NF-κB activation is associated with resistance to apoptosis. Following stimulation with UV light however, NF-κB activation has been shown to be required for programmed cell death. To study this effect further and to determine the relationship between NF-κB and p53 function, we have examined the effect of UV light on U2OS cells. UV stimulation resulted in the activation of NF-κB DNA-binding and the induction of p53. Surprisingly, and in contrast with tumour necrosis factor α stimulation, this UV-induced NF-κB was transcriptionally inert. These observations suggest a model in which the NF-κB switch from an anti-apoptotic to a pro-apoptotic role within the cell results from modulation of its ability to stimulate gene expression, possibly as a result of the ability of p53 to sequester transcriptional co-activator proteins such as p300/CREB (cAMP-response-element-binding protein)-binding protein.

scholarly journals The effect of low LET (Linear Energy Transfer) ionizing radiation to catalase activity of wistar’s submandibular gland

2016 ◽  
Vol 1 (3) ◽  
pp. 145
Author(s):  
Nevy T. Putri ◽  
Sarianoferni Sarianoferni ◽  
Endah Wahjuningsih
Keyword(s):  
Energy Transfer ◽  
Ionizing Radiation ◽  
Submandibular Gland ◽  
Rattus Norvegicus ◽  
Catalase Activity ◽  
Linear Energy Transfer ◽  
Submandibular Salivary Gland ◽  
X Rays ◽  
X Ray ◽  
Bonferroni Test

Intraoral periapical radiograph examination is the additional examination which is the most widely used in Dentistry. This radiograph examination using an x-ray ionizing radiation with low LET (Linear Energy Transfer), and may affect submandibular salivary gland. Ionizing radiation exposure can cause damage by inducing a series of changes at the molecular and cellular level. This study aimed to prove the effects of x-ray ionizing radiation with low LET towards the catalase activity of Rattus norvegicus strain Wistar’s submandibular gland. The subjects were 28 male Wistar rats and divided into 4 groups (n=7). Three groups were exposed 4, 8 and 14 times to radiation with 0.002 µSv for each exposure. The catalase activity of each rat was examined by a spectrophotometer. Data were analyzed using one-way ANOVA followed by Bonferroni test. The results showed the average of catalase activity on Wistar rat’s submandibular gland, respectively for: 0.150±0.0895 (KK), 0.1405±0.0607 (K1), 0.1228±0.0290 (K2), 0.1227±0.0556 (K3). Data showed significant differences of catalase activity between test groups, but showed not significant differences of catalase activity between each groups of Rattus norvegicus strain Wistar’s submandibular gland. In this study concluded decreased catalase activity of Rattus norvegicus strain Wistar’s submandibular gland resulting from x-rays ionizing radiation by 4 times, 8 times and 14 times exposures.

In VitroEvaluation of Combined Temozolomide and Radiotherapy Using X Rays and High-Linear Energy Transfer Radiation for Glioblastoma

2012 ◽  
Vol 177 (5) ◽  
pp. 651-662 ◽  
Author(s):  
Lara Barazzuol ◽  
Raj Jena ◽  
Neil G. Burnet ◽  
Jonathan C. G. Jeynes ◽  
Michael J. Merchant ◽  
...  
Keyword(s):  
Energy Transfer ◽  
Linear Energy Transfer ◽  
X Rays ◽  
Linear Energy Transfer Radiation ◽  
High Linear Energy Transfer

Responses of synchronous L5178Y S/S cells to heavy ions and their significance for radiobiological theory

1989 ◽  
Vol 237 (1286) ◽  
pp. 27-42 ◽  
Keyword(s):  
Cell Cycle ◽  
Energy Transfer ◽  
Linear Energy Transfer ◽  
Relative Biological Effectiveness ◽  
Survival Curve ◽  
Heavy Ion ◽  
Ion Beams ◽  
X Rays ◽  
Biological Effectiveness ◽  
Ionizing Radiations

Synchronous suspensions of the radiosensitive S/S variant of the L5178Y murine leukaemic lymphoblast at different positions in the cell cycle were exposed aerobically to segments of heavy-ion beams ( 20 Ne, 28 Si, 40 Ar, 56 Fe and 93 Nb) in the Bragg plateau regions of energy deposition. The incident energies of the ion beams were in the range of 460 ± 95 MeV u -1 , and the calculated values of linear energy transfer (LET ∞ ) for the primary nuclei in the irradiated samples were 33 ± 3, 60 ± 3, 95 ± 5, 213 ± 21 and 478 ± 36 keV μm -1 , respectively; 280 kVp X-rays were used as the baseline radiation. Generally, the maxima or inflections in relations between relative biological effectiveness (RBE) and LET ∞ were dependent upon the cycle position at which the cells were irradiated. Certain of those relations were influenced by post-irradiation hypothermia. Irradiation in the cell cycle at mid -G 1 to mid-G 1 +3 h, henceforth called G 1 to G 1 + 3 h, resulted in survival curves that were close approximations to simple exponential functions. As the LET ∞ was increased, the RBE did not exceed 1.0, and by 478 keV μm -1 it had fallen to 0.39. Although similar behaviour has been reported for inactivation of proteins and certain viruses by ionizing radiations, so far the response of the S/S variant is unique for mammalian cells. The slope of the survival curve for X-photons ( D 0 :0.27 Gy) is reduced in G 1 to G 1 + 3 h by post-irradiation incubation at hypothermic temperatures and reaches a minimum ( D 0 : 0.51 Gy) at 25 °C. As the LET ∞ was increased, however, the extent of hypothermic recovery was reduced progressively and essentially was eliminated at 478 keV μm -1 . At the cycle position where the peak of radioresistance to X-photons occurs for S/S cells, G 1 + Sh, increases in LET ∞ elicited only small increases in RBE (at 10% survival), until a maximum was reached around 200 keV μm -1 . At 478 keV μm -1 , what little remained of the variation in response through the cell cycle could be attributed to secondary radiations (δ rays) and smaller nuclei produced by fragmentation of the primary ions. Definitions 1. Linear energy transfer (LET ∞ ) is the energy deposited per unit length of track by an ionizing particle and usually is measured in kiloelectron volts per micrometer (in water). 2. Penumbra . Atomic interactions along the track of a heavy ion result in the ejection of electrons with energies sufficient to move beyond the region of dense ionization which constitutes the track core, and so may be considered to form a penumbra of sparsely ionizing radiations around the track core. 3. RBE . The effectiveness of a densely ionizing radiation (heavy ion) compared to a sparsely ionizing radiation, e. g. X- or γ -photons, is measured by the inverse ratio of the doses of each radiation needed to produce a given radiobiological effect, and is known as the relative biological effectiveness (RBE): the usual reference radiation is 250 kVp X-rays. 4. D 0 is a measure of the radiosensitivity of a cell as determined from the (limiting) linear slope of the survival curve, and is the dose in Gray (1 Gy ≡ 1 Joule kg -1 ) required to reduce the survival at a point anywhere in that region of the survival curve to 37% of its value at that point.

Experimental Linear Energy Transfer of Heavy Ions in Silicon for RADEF Cocktail Species

2009 ◽  
Vol 56 (4) ◽  
pp. 2242-2246 ◽  
Author(s):  
A. Javanainen ◽  
M. Sillanpaa ◽  
W. H. Trzaska ◽  
A. Virtanen ◽  
G. Berger ◽  
...  
Keyword(s):  
Energy Transfer ◽  
Linear Energy Transfer ◽  
Heavy Ions

scholarly journals Anti-Oxidative, Anti-Inflammatory and Anti-Apoptotic Effects of Flavonols: Targeting Nrf2, NF-ҡB and p53 Pathways in Neurodegeneration

Antioxidants ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1628
Author(s):  
Maja Jazvinšćak Jembrek ◽  
Nada Oršolić ◽  
Lucija Mandić ◽  
Anja Sadžak ◽  
Suzana Šegota
Keyword(s):  
Transcription Factors ◽  
Cellular Response ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Nuclear Factor Κb ◽  
Related Factor ◽  
Nuclear Factor ◽  
Anti Inflammatory ◽  
New Treatments ◽  
Apoptotic Effects

Neurodegenerative diseases are one of the leading causes of disability and death worldwide. Intracellular transduction pathways that end in the activation of specific transcription factors are highly implicated in the onset and progression of pathological changes related to neurodegeneration, of which those related to oxidative stress (OS) and neuroinflammation are particularly important. Here, we provide a brief overview of the key concepts related to OS- and neuroinflammation-mediated neuropathological changes in neurodegeneration, together with the role of transcription factors nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor-κB (NF-κB). This review is focused on the transcription factor p53 that coordinates the cellular response to diverse genotoxic stimuli, determining neuronal death or survival. As current pharmacological options in the treatment of neurodegenerative disease are only symptomatic, many research efforts are aimed at uncovering efficient disease-modifying agents. Natural polyphenolic compounds demonstrate powerful anti-oxidative, anti-inflammatory and anti-apoptotic effects, partially acting as modulators of signaling pathways. Herein, we review the current understanding of the therapeutic potential and limitations of flavonols in neuroprotection, with emphasis on their anti-oxidative, anti-inflammatory and anti-apoptotic effects along the Nrf2, NF-κB and p53 pathways. A better understanding of cellular and molecular mechanisms of their action may pave the way toward new treatments.

BIOLOGICAL EFFECTIVENESS OF FAST NEUTRONS AND ACCELERATED MULTICHARGED IONS FOR DERIVATION OF A NEW DEPENDENCE OF SPACE RADIATION QUALITY COEFFICIENTS ON LINEAR ENERGY TRANSFER

2021 ◽  
Vol 55 (3) ◽  
pp. 5-15
Author(s):  
A.V. Shafirkin ◽  
◽  
Yu.G. Grigoriev ◽  
I.B. Ushakov ◽  
V.A. Shurshakov ◽  
...  
Keyword(s):  
Energy Transfer ◽  
Linear Energy Transfer ◽  
Cell Transformation ◽  
Risk Mitigation ◽  
Radiation Risk ◽  
Galactic Cosmic Rays ◽  
Fast Neutrons ◽  
Recent Experimental Data ◽  
Radiation Quality ◽  
Biological Effectiveness

The authors review recent experimental data about relative biological effectiveness (RBE) of low absorbed doses (0.01–0.5 Gy) from fast neutrons and accelerated multicharged ions currently accepted as career limits for cosmonauts from the standpoint of late effects risk mitigation. According to the new radiobiological findings, literary maximum values of the RBEM coefficients for low doses and dose rates are increased two or three times for late cytogenetic effects; benign cell transformation and tumor risks; lifetime reduction; disorders in the brain cortex neurons and damages to organs; lenticular opacity and cataract. The analysis-based revision of the quality coefficients – linear energy transfer (LET) relationship leads to a considerable increase of equivalent doses received from galactic cosmic rays and fast neutrons, and calculated total radiation risk over cosmonaut's lifetime.

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