Nuclear accumulation of cyclin D1 following long-term fractionated exposures to low-dose ionizing radiation in normal human diploid cells

Shimura, Tsutomu; Hamada, Nobuyuki; Sasatani, Megumi; Kamiya, Kenji; Kunugita, Naoki

doi:10.4161/cc.28139

Cited by 20 publications

(38 citation statements)

References 29 publications

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“…The resulting abnormal nuclear retention of cyclin D1 induced genomic instability in long-term FR irradiated cells. [10][11][12] In contrast, NSCs showed the lack of effects on induction of mitochondrial activity by long-term FR. These cells exhibited efficient DNA repair during FR exposure intervals and resistance to long-term FR as evident by no g-H2AX and RAD51 foci.…”

Section: Resistance To Long-term Fr In Nscsmentioning

confidence: 82%

“…As we previously reported that cells continued to grow exponentially for 31 d if exposed to 0.01 or 0.05 Gy FR. 12 The histograms of cellular DNA content indicated that long-term FR had a negligible effect on IR-induced G2-arrest in TIG-3, MRC-5, and NSCs (Fig. 7A).…”

Section: Cell Cycle Arrest and Cellular Senescence Induced By Sr At Hmentioning

confidence: 99%

“…12,29 Cells were fixed with 4% formaldehyde for 10 min and permeabilized with 0.5% Triton X-100 for 5 min. For double staining with MitoTraker deep red (Invitrogen) and parkin, cells were fixed with 4% formaldehyde for 15 min and permeabilized with 0.2% Triton X-100 for 10 min.…”

Section: Immunofluorescencementioning

confidence: 99%

“…11 Elevated levels of mitochondrial ROS disturb cell cycle signaling via protein oxidation and induce genomic instability due to nuclear cyclin D1 retention in long-term low-dose irradiated cells. 12 Additionally, Ca 2C /calcineurin-mediated retrograde signaling from mitochondria to nucleus may cause epigenetic changes in the nuclear DNA (nDNA). 13 Mitochondrial ROS can damage nDNA leading to genomic instability in the cells.…”

Section: Introductionmentioning

confidence: 99%

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A comparison of radiation-induced mitochondrial damage between neural progenitor stem cells and differentiated cells

et al. 2017

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Mitochondria play a key role in maintaining cellular homeostasis during stress responses, and mitochondrial dysfunction contributes to carcinogenesis, aging, and neurologic disease. We here investigated ionizing radiation (IR)-induced mitochondrial damage in human neural progenitor stem cells (NSCs), their differentiated counterparts and human normal fibroblasts. Long-term fractionated radiation (FR) with low doses of X-rays for 31 d enhanced mitochondrial activity as evident by elevated mitochondrial membrane potential (DCm) and mitochondrial complex IV (cytochrome c oxidase) activity to fill the energy demands for the chronic DNA damage response in differentiated cells. Subsequent reduction of the antioxidant glutathione via continuous activation of mitochondrial oxidative phosphorylation caused oxidative stress and genomic instability in differentiated cells exposed to longterm FR. In contrast, long-term FR had no effect on the mitochondrial activity in NSCs. This cell type showed efficient DNA repair, no mitochondrial damage, and resistance to long-term FR. After high doses of acute single radiation (SR) (> 5 Gy), cell cycle arrest at the G2 phase was observed in NSCs and human fibroblasts. Under this condition, increase in mitochondria mass, mitochondrial DNA, and intracellular reactive oxygen species (ROS) levels were observed in the absence of enhanced mitochondrial activity. Consequently, cellular senescence was induced by high doses of SR in differentiated cells.In conclusion, we demonstrated that mitochondrial radiation responses differ according to the extent of DNA damage, duration of radiation exposure, and cell differentiation.

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Section: Resistance To Long-term Fr In Nscsmentioning

confidence: 82%

Section: Cell Cycle Arrest and Cellular Senescence Induced By Sr At Hmentioning

confidence: 99%

Section: Immunofluorescencementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A comparison of radiation-induced mitochondrial damage between neural progenitor stem cells and differentiated cells

et al. 2017

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“…Immunofluorescence staining was performed as previously described (26,27). Briefly, the cells were seeded onto 18 3 18-mm coverslips, placed in 35-mm tissue culture dishes, and cultured overnight.…”

Section: Immunofluorescencementioning

confidence: 99%

Epicatechin as a promising agent to countermeasure radiation exposure by mitigating mitochondrial damage in human fibroblasts and mouse hematopoietic cells

et al. 2019

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Accidental radiation exposure that is due to a nuclear accident or terrorism using radioactive materials has severe detrimental effects on human health, and it can manifest as acute radiation syndrome depending on the dose and distribution of the radiation. Therefore, the development of radiation countermeasure agents is urgently needed to protect humans against radiation injury. Besides nuclear DNA, the mitochondria are important targets of ionizing radiation (IR) because these organelles generate reactive oxygen species (ROS). Recently, we revealed that mitochondrial ROS‐activated cell signaling is associated with IR‐induced tumor formation. Here, we investigated the effectiveness of ascorbic acid and epicatechin (EC) in scavenging ROS as radiation countermeasure agents by using human cells and mouse. Preradiation and postradiation treatments with EC mitigate ROS‐mediated mitochondrial damage, IR‐induced oxidative stress responses including reduction of superoxide dismutase activity, and elevated nuclear factor erythroid 2–related factor 2 expression, and they improve human fibroblast survival. As well as in vitro, EC mitigated ROS‐mediated mitochondrial damage after exposure to IR in vivo in mouse platelets. Furthermore, oral administration of EC significantly enhanced the recovery of mouse hematopoietic cells from radiation injury in vivo. In summary, EC is a potentially viable countermeasure agent that is immediately effective against accidental IR exposure by targeting mitochondria‐mediated oxidative stress.—Shimura, T., Koyama, M., Aono, D., Kunugita, N. Epicatechin as a promising agent to countermeasure radiation exposure by mitigating mitochondrial damage in human fibroblasts and mouse hematopoietic cells. FASEB J. 33, 6867–6876 (2019). http://www.fasebj.org

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Dynamic expression of FAM83D in peripheral organs at different ages in mice

Qi-xian

Zhou

et al. 2021

Gene Expression Patterns

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Nuclear accumulation of cyclin D1 following long-term fractionated exposures to low-dose ionizing radiation in normal human diploid cells

Cited by 20 publications

References 29 publications

A comparison of radiation-induced mitochondrial damage between neural progenitor stem cells and differentiated cells

A comparison of radiation-induced mitochondrial damage between neural progenitor stem cells and differentiated cells

Epicatechin as a promising agent to countermeasure radiation exposure by mitigating mitochondrial damage in human fibroblasts and mouse hematopoietic cells

Dynamic expression of FAM83D in peripheral organs at different ages in mice

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