Mechanism of turnover or persistence of radiation-induced myofibroblast in vitro

Shimura, Tsutomu; Ando, Takahito; Narao, Momoka; Sasatani, Megumi; Kamiya, Kenji; Ushiyama, Akira

doi:10.1080/15384101.2020.1848063

Cited by 10 publications

(16 citation statements)

References 23 publications

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“…The fluorescence of DCFDA indicates oxidation by hydrogen peroxide, peroxynitrite or hydroxyl radical. The effect of serum concentration on the radiation-induced oxidative stress was repored by using DCFDA staining in human fiboroblasts [ 13 ]. However, DCFDA staining cannot distinguish specific types of ROS [ 23 , 24 ].…”

Section: Resultsmentioning

confidence: 99%

“…Transiently increased levels of GSH following whole-body irradiation to mouse is associated with the elevation of natural killer (NK) activity in mouse splenocytes [ 12 ]. Radiation induces mitochondrial change, including activation of OXPHOS, generation of ROS, mitochondrial Parkin staining and induction of mitochondrial biogenesis in terms of oxidative stress responses in human fibroblasts [ 4 , 13–15 ]. Mitochondria are vulnerable to radiation-induced effects because they are the sites of ROS generation.…”

Section: Introductionmentioning

confidence: 99%

“…Reduce in serum concentration enhanced radiation-induced late ROS accumulation which was detected by using 2′, 7′-dichlorofluorescin diacetate (DCFDA) in human fiboroblasts. ROS appeared by exposure to irradiation with any doses even at low doses in the growth-restricted conditions in which cells were cultured in 0.5% or 0% fetal calf serum (FCS), while this occurred only by exposure to ≥5 Gy of single-radiation (SR) under standard serum condition (10% FCS) [ 13 ]. Thus, serum starvation or serum deprivation elevates baseline oxidative stress compared to that in standard serum condition (10% FCS) [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

“…ROS appeared by exposure to irradiation with any doses even at low doses in the growth-restricted conditions in which cells were cultured in 0.5% or 0% fetal calf serum (FCS), while this occurred only by exposure to ≥5 Gy of single-radiation (SR) under standard serum condition (10% FCS) [ 13 ]. Thus, serum starvation or serum deprivation elevates baseline oxidative stress compared to that in standard serum condition (10% FCS) [ 13 ]. Interaction between tumor-associated stromal cells and tumor cells makes tumor microenvironment formation which plays an important role in the initiation and progression of cancer [ 18–20 ].…”

Section: Introductionmentioning

confidence: 99%

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Radiation affects glutathione redox reaction by reduced glutathione peroxidase activity in human fibroblasts

Shimura

Nakashiro

Fujiwara

et al. 2021

Journal of Radiation Research

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The glutathione (GSH) redox control is critical to maintain redox balance in the body’s internal environment, and its perturbation leads to a dramatic increase in reactive oxygen species (ROS) levels and oxidative stress which have negative impacts on human health. Although ionizing radiation increases mitochondrial ROS generation, the mechanisms underlying radiation-induced late ROS accumulation are not fully understood. Here we investigated the radiation effect on GSH redox reactions in normal human diploid lung fibroblasts TIG-3 and MRC-5. Superoxide anion probe MitoSOX-red staining and measurement of GSH peroxidase (GPx) activity revealed that high dose single-radiation (SR) exposure (10 Gy) increased mitochondrial ROS generation and overall oxidative stress in parallel with decrease in GSH peroxidase (GPx) activity, while GSH redox control was effective after exposure to moderate doses under standard serum conditions. We used different serum conditions to elucidate the role of serum on GSH redox reaction. Serum starvation, serum deprivation and DNA damage response (DDR) inhibitors-treatment reduced the GPx activity and increased mitochondrial ROS generation regardless of radiation exposure. Fractionated-radiation was used to evaluate the radiation effect on GSH reactions. Repeated fractionated-radiation induced prolonged oxidative stress by down-regulation of GPx activity. In conclusion, radiation affects GSH usage according to radiation dose, irradiation methods and serum concentration. Radiation affected the GPx activity to disrupt fibroblast redox homeostasis.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Radiation affects glutathione redox reaction by reduced glutathione peroxidase activity in human fibroblasts

Shimura

Nakashiro

Fujiwara

et al. 2021

Journal of Radiation Research

Self Cite

View full text Add to dashboard Cite

show abstract

“…Cellular antioxidant defense systems maintain ROS levels after exposure to low-to-moderate doses of ionizing radiation. Acute single radiation (SR) of less than 2 Gy transiently increases ROS concentrations, which subsequently return to baseline levels 24 h after irradiation, in human fibroblasts [ 32 , 33 ]. In contrast, high doses of radiation (more than 5 Gy) are associated with the induction of oxidative stress, suggesting that the antioxidant defense system is ineffective in this scenario.…”

Section: Radiation-induced Oxidative Stressmentioning

confidence: 99%

ATM-Mediated Mitochondrial Radiation Responses of Human Fibroblasts

Shimura

2021

Genes

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Ataxia telangiectasia (AT) is characterized by extreme sensitivity to ionizing radiation. The gene mutated in AT, Ataxia Telangiectasia Mutated (ATM), has serine/threonine protein kinase activity and mediates the activation of multiple signal transduction pathways involved in the processing of DNA double-strand breaks. Reactive oxygen species (ROS) created as a byproduct of the mitochondria’s oxidative phosphorylation (OXPHOS) has been proposed to be the source of intracellular ROS. Mitochondria are uniquely vulnerable to ROS because they are the sites of ROS generation. ROS-induced mitochondrial mutations lead to impaired mitochondrial respiration and further increase the likelihood of ROS generation, establishing a vicious cycle of further ROS production and mitochondrial damage. AT patients and ATM-deficient mice display intrinsic mitochondrial dysfunction and exhibit constitutive elevations in ROS levels. ATM plays a critical role in maintaining cellular redox homeostasis. However, the precise mechanism of ATM-mediated mitochondrial antioxidants remains unclear. The aim of this review paper is to introduce our current research surrounding the role of ATM on maintaining cellular redox control in human fibroblasts. ATM-mediated signal transduction is important in the mitochondrial radiation response. Perturbation of mitochondrial redox control elevates ROS which are key mediators in the development of cancer by many mechanisms, including ROS-mediated genomic instability, tumor microenvironment formation, and chronic inflammation.

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Mechanisms of radiation‐induced tissue damage and response

Zhou,

Zhu,

Liu

et al. 2024

MedComm

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Radiation‐induced tissue injury (RITI) is the most common complication in clinical tumor radiotherapy. Due to the heterogeneity in the response of different tissues to radiation (IR), radiotherapy will cause different types and degrees of RITI, which greatly limits the clinical application of radiotherapy. Efforts are continuously ongoing to elucidate the molecular mechanism of RITI and develop corresponding prevention and treatment drugs for RITI. Single‐cell sequencing (Sc‐seq) has emerged as a powerful tool in uncovering the molecular mechanisms of RITI and for identifying potential prevention targets by enhancing our understanding of the complex intercellular relationships, facilitating the identification of novel cell phenotypes, and allowing for the assessment of cell heterogeneity and spatiotemporal developmental trajectories. Based on a comprehensive review of the molecular mechanisms of RITI, we analyzed the molecular mechanisms and regulatory networks of different types of RITI in combination with Sc‐seq and summarized the targeted intervention pathways and therapeutic drugs for RITI. Deciphering the diverse mechanisms underlying RITI can shed light on its pathogenesis and unveil new therapeutic avenues to potentially facilitate the repair or regeneration of currently irreversible RITI. Furthermore, we discuss how personalized therapeutic strategies based on Sc‐seq offer clinical promise in mitigating RITI.

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Mechanism of turnover or persistence of radiation-induced myofibroblast in vitro

Cited by 10 publications

References 23 publications

Radiation affects glutathione redox reaction by reduced glutathione peroxidase activity in human fibroblasts

Radiation affects glutathione redox reaction by reduced glutathione peroxidase activity in human fibroblasts

ATM-Mediated Mitochondrial Radiation Responses of Human Fibroblasts

Mechanisms of radiation‐induced tissue damage and response

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