Nitric oxide-mediated bystander signal transduction induced by heavy-ion microbeam irradiation

Tomita, Masaru; Matsumoto, Hideki; Funayama, Tomoo; Yokota, Yuichiro; Otsuka, Kensuke; Maeda, Munetoshi; Kobayashi, Yasuhiko

doi:10.1016/j.lssr.2015.06.004

Cited by 18 publications

(18 citation statements)

References 48 publications

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“…While C ions (LET = 33 and 73 keV/µm) and X rays had comparable potential to activate NF-κB in human embryonic kidney cells [42], Ar (LET = 272 keV/µm) and Ne (LET = 91 keV/µm) ions produced the highest relative biological effectiveness (RBE) of 8.9 [39]. In normal human fibroblasts exposed to Ar microbeam particles, phosphorylation of NF-κB was also observed in the non-exposed cells as a result of nitric oxide-mediated bystander effects [85]. NF-κB has been demonstrated to play a key role in radiation-induced bystander effects [86], but such studies are beyond the scope of this review.…”

Section: Effects Of Space Radiation Exposure On Nf-κbmentioning

confidence: 99%

Transcriptomics, NF-κB Pathway, and Their Potential Spaceflight-Related Health Consequences

Zhang

Moreno‐Villanueva

Krieger

et al. 2017

IJMS

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In space, living organisms are exposed to multiple stress factors including microgravity and space radiation. For humans, these harmful environmental factors have been known to cause negative health impacts such as bone loss and immune dysfunction. Understanding the mechanisms by which spaceflight impacts human health at the molecular level is critical not only for accurately assessing the risks associated with spaceflight, but also for developing effective countermeasures. Over the years, a number of studies have been conducted under real or simulated space conditions. RNA and protein levels in cellular and animal models have been targeted in order to identify pathways affected by spaceflight. Of the many pathways responsive to the space environment, the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) network appears to commonly be affected across many different cell types under the true or simulated spaceflight conditions. NF-κB is of particular interest, as it is associated with many of the spaceflight-related health consequences. This review intends to summarize the transcriptomics studies that identified NF-κB as a responsive pathway to ground-based simulated microgravity or the true spaceflight condition. These studies were carried out using either human cell or animal models. In addition, the review summarizes the studies that focused specifically on NF-κB pathway in specific cell types or organ tissues as related to the known spaceflight-related health risks including immune dysfunction, bone loss, muscle atrophy, central nerve system (CNS) dysfunction, and risks associated with space radiation. Whether the NF-κB pathway is activated or inhibited in space is dependent on the cell type, but the potential health impact appeared to be always negative. It is argued that more studies on NF-κB should be conducted to fully understand this particular pathway for the benefit of crew health in space.

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Section: Effects Of Space Radiation Exposure On Nf-κbmentioning

confidence: 99%

Transcriptomics, NF-κB Pathway, and Their Potential Spaceflight-Related Health Consequences

Zhang

Moreno‐Villanueva

Krieger

et al. 2017

IJMS

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“…The results demonstrate that bystander communication of DNA damage involves connexin signaling via gap junctions and hemichannels, the canonical IP 3 /Ca 2+ signaling cascade, extracellular ATP, and ROS/NO signaling. Each of these signals has been implicated in radiation-induced bystander signaling 38,39,[46][47][48][49][50] , but a coherent framework is currently lacking. Of note, most of these signals play a role in cell-cell communication of Ca 2+ signals 51 and all of them have been linked to hemichannels, either as a trigger for their opening 14,40,52,53 or as a substance released in a manner facilitated by hemichannels 54,55 .…”

Section: Discussionmentioning

confidence: 99%

“…6e). NO is involved in the response to ionizing radiation 33,39 as well as in hemichannel opening 40,41 and we further tested the effect of NO scavenging by preloading the cells with C-PTIO (100 μM; 30 min prior to 1 Gy irradiation); this strongly reduced irradiation-induced ATP release (Fig. 6e) while having no effect on gap junctional coupling (Supplementary Fig.…”

Section: Irradiation-induced Intracellular Ca 2+ Elevation and Ros Prmentioning

confidence: 99%

Cx43 channels and signaling via IP3/Ca2+, ATP, and ROS/NO propagate radiation-induced DNA damage to non-irradiated brain microvascular endothelial cells

et al. 2020

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Radiotherapeutic treatment consists of targeted application of radiation beams to a tumor but exposure of surrounding healthy tissue is inevitable. In the brain, ionizing radiation induces breakdown of the blood-brain barrier by effects on brain microvascular endothelial cells. Damage from directly irradiated cells can be transferred to surrounding non-exposed bystander cells, known as the radiation-induced bystander effect. We investigated involvement of connexin channels and paracrine signaling in radiation-induced bystander DNA damage in brain microvascular endothelial cells exposed to focused X-rays. Irradiation caused DNA damage in the directly exposed area, which propagated over several millimeters in the bystander area. DNA damage was significantly reduced by the connexin channel-targeting peptide Gap26 and the Cx43 hemichannel blocker TAT-Gap19. ATP release, dye uptake, and patch clamp experiments showed that hemichannels opened within 5 min post irradiation in both irradiated and bystander areas. Bystander signaling involved cellular Ca 2+ dynamics and IP 3 , ATP, ROS, and NO signaling, with Ca 2+ , IP 3 , and ROS as crucial propagators of DNA damage. We conclude that bystander effects are communicated by a concerted cascade involving connexin channels, and IP 3 /Ca 2+ , ATP, ROS, and NO as major contributors of regenerative signal expansion.

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“…Bystander studies using normal human fibroblasts were performed with the focus of attention on various endpoints, such as cell survival rate, frequency of micronucleus formation, phosphorylation of histone H2AX, apoptosis, and induction of p53 protein [34][35][36][37][38][39]. Moreover, gene expression analysis of bystander cells using the DNA microarray assay revealed that the G protein/PI-3 kinase pathways were activated in the bystander cells but not in directly irradiated cells [40].…”

Section: Programmed Matrix Irradiation Without Targeting Specific Cellsmentioning

confidence: 99%

Heavy-Ion Microbeams for Biological Science: Development of System and Utilization for Biological Experiments in QST-Takasaki

Funayama

2019

QuBS

Self Cite

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Target irradiation of biological material with a heavy-ion microbeam is a useful means to analyze the mechanisms underlying the effects of heavy-ion irradiation on cells and individuals. At QST-Takasaki, there are two heavy-ion microbeam systems, one using beam collimation and the other beam focusing. They are installed on the vertical beam lines of the azimuthally-varying-field cyclotron of the TIARA facility for analyzing heavy-ion radiation effects on biological samples. The collimating heavy-ion microbeam system is used in a wide range of biological research not only in regard to cultured cells but also small individuals, such as silkworms, nematode C. elegans, and medaka fish. The focusing microbeam system was designed and developed to perform more precise target irradiation that cannot be achieved through collimation. This review describes recent updates of the collimating heavy ion microbeam system and the research performed using it. In addition, a brief outline of the focusing microbeam system and current development status is described.

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Nitric oxide-mediated bystander signal transduction induced by heavy-ion microbeam irradiation

Cited by 18 publications

References 48 publications

Transcriptomics, NF-κB Pathway, and Their Potential Spaceflight-Related Health Consequences

Transcriptomics, NF-κB Pathway, and Their Potential Spaceflight-Related Health Consequences

Cx43 channels and signaling via IP3/Ca2+, ATP, and ROS/NO propagate radiation-induced DNA damage to non-irradiated brain microvascular endothelial cells

Heavy-Ion Microbeams for Biological Science: Development of System and Utilization for Biological Experiments in QST-Takasaki

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