The Absence of an Early Calcium Response to Heavy-Ion Radiation in Mammalian Cells

Du, Guohao; Fischer, B.; Voss, Kay-O.; Becker, Gudrun; Taucher-Scholz, G.; Kraft, Gerhard; Thiel, Gerhard

doi:10.1667/rr1270.1

Cited by 13 publications

(4 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This delay is well beyond the life-time of oxygen radicals including the long lived H 2 O 2 (40, 41) meaning that Ca 2+ oscillations are not initiated by radiolysis of water or peroxidation/oxidation of lipids/proteins. This lack of an immediate impact of IR on Ca 2+ cyt is consistent with previous high-resolution imaging experiments which showed that individual high energy ions had no immediate impact on the Ca 2+ concentration along the track of the ions (42). The current data are not sufficient to explain the gap between IR exposure and the onset of Ca 2+ cyt oscillations.…”

Section: Discussionsupporting

confidence: 91%

X-ray Irradiation activates immune response in human T-lymphocytes by eliciting a Ca²⁺signaling cascade

Thiel

Tandl

Sponagel

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

Radiation therapy is efficiently employed for eliminating cancer cells and reducing tumor growth. To further improving its therapeutic application it is mandatory to unravel the molecular effects of ionizing irradiation and to understand whether they support or counteract tumor therapy. Here we examine the impact of X-ray irradiation on immune activation of human T cells with single doses typically employed in tumor therapy. We discover that exposing cells to radiation triggers in a population of leukemic Jurkat T cells and in peripheral blood mononuclear cells (PBMCs) a canonical Ca2+ signaling cascade, which elicits immune activation of these cells. An early step in the signaling cascade is the initiation of sustained oscillations of the cytosolic Ca2+ concentration, an event mediated by store operated Ca2+ entry (SOCE) via an X-ray induced clustering of the Calcium Release-Activated Calcium Modulator 1 with the stromal interaction molecule 1 (Oari1/STIM1). A functional consequence of the Ca2+ signaling cascade is the translocation of the transcription factor nuclear factor of activated T cells (NFAT) from the cytosol into the nucleus where it elicits the expression of genes required for immune activation. These data imply that a direct activation of blood immune cells by ionizing irradiation has an impact on toxicity and therapeutic effects of radiation therapy.

show abstract

Section: Discussionsupporting

confidence: 91%

X-ray Irradiation activates immune response in human T-lymphocytes by eliciting a Ca²⁺signaling cascade

Thiel

Tandl

Sponagel

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…through natural background radiation or medical applications. So far, however, only few facilities have been described that combine ionizing microirradiation with online live-cell microscopy [9], [10], [11], [12], [13]. At the Munich ion microbeam facility SNAKE ( s uperconducting n anoprobe for a pplied nuclear (German: k ern-) physics e xperiments), microirradiation of cells at submicrometer resolution [14] is combined with online fluorescence microscopy [10] to allow for the analysis of protein recruitment at damage sites induced by transversal of ions.…”

Section: Introductionmentioning

confidence: 99%

Recruitment Kinetics of DNA Repair Proteins Mdc1 and Rad52 but Not 53BP1 Depend on Damage Complexity

et al. 2012

View full text Add to dashboard Cite

The recruitment kinetics of double-strand break (DSB) signaling and repair proteins Mdc1, 53BP1 and Rad52 into radiation-induced foci was studied by live-cell fluorescence microscopy after ion microirradiation. To investigate the influence of damage density and complexity on recruitment kinetics, which cannot be done by UV laser irradiation used in former studies, we utilized 43 MeV carbon ions with high linear energy transfer per ion (LET = 370 keV/µm) to create a large fraction of clustered DSBs, thus forming complex DNA damage, and 20 MeV protons with low LET (LET = 2.6 keV/µm) to create mainly isolated DSBs. Kinetics for all three proteins was characterized by a time lag period T0 after irradiation, during which no foci are formed. Subsequently, the proteins accumulate into foci with characteristic mean recruitment times τ1. Mdc1 accumulates faster (T0 = 17±2 s, τ1 = 98±11 s) than 53BP1 (T0 = 77±7 s, τ1 = 310±60 s) after high LET irradiation. However, recruitment of Mdc1 slows down (T0 = 73±16 s, τ1 = 1050±270 s) after low LET irradiation. The recruitment kinetics of Rad52 is slower than that of Mdc1, but exhibits the same dependence on LET. In contrast, the mean recruitment time τ1 of 53BP1 remains almost constant when varying LET. Comparison to literature data on Mdc1 recruitment after UV laser irradiation shows that this rather resembles recruitment after high than low LET ionizing radiation. So this work shows that damage quality has a large influence on repair processes and has to be considered when comparing different studies.

show abstract

“…The proliferation and activation of CFs, as well as the increased ECM, are important mechanisms of myocardial fibrosis (23). Intracellular calcium is an important second messenger and the driving force of CF activation (24,25). Studies by our group (26) and other research groups (12,27) have demonstrated that the increase or activation of CaSR expression increases intracellular calcium through the G protein/phospholipase C/inositol triphosphate pathway.…”

Section: Discussionmentioning

confidence: 99%

Calcium‑sensing receptor promotes high glucose‑induced myocardial fibrosis via upregulation of the TGF‑β1/Smads pathway in cardiac fibroblasts

et al. 2019

View full text Add to dashboard Cite

Diabetic cardiomyopathy (DCM) is a major complication of diabetes and myocardial fibrosis is its major pathological feature. Calcium-sensing receptor (CaSR) is a G protein-coupled receptor and participates in the regulation of calcium homeostasis; it is implicated in a range of diseases, including myocardial ischemia/reperfusion injury, myocardial infarction and pulmonary hypertension. However, whether CaSR is associated with myocardial fibrosis in DCM has remained elusive. In the present study, type 1 diabetic (T1D) rats and primary neonatal rat cardiac fibroblasts (CFs) were used to observe changes in CaSR to assess its potential as an indicator of myocardial fibrosis. The in vivo experiments revealed that in the T1D and CaSR agonist (R568) groups, evident collagen (Col)-I and -III deposition was present after 12 weeks. Furthermore, the in vitro experiment indicated that the levels of transforming growth factor (TGF)-β 1 , phosphorylated (p-) protein kinase C, p-p38, p-Smad2, TβRI, TβRII, along with the intracellular Ca 2+ levels and the content of TGF-β 1 in the culture medium were significantly increased in a high-glucose (HG) group and an R568-treated group. Treatment with the CaSR inhibitor Calhex231 significantly inhibited the abovementioned changes. Collectively, the results indicated that the increase of CaSR expression in CFs may induce intracellular Ca 2+ increases and the activation of TGF-β 1 /Smads, and enhance the proliferation of CFs, along with the excessive deposition of Col, resulting in myocardial fibrosis. The present results indicate an important novel mechanism for HG-induced myocardial fibrosis and suggest that CaSR may be a promising potential therapeutic target for DCM.

show abstract

The Absence of an Early Calcium Response to Heavy-Ion Radiation in Mammalian Cells

Cited by 13 publications

References 33 publications

X-ray Irradiation activates immune response in human T-lymphocytes by eliciting a Ca²⁺signaling cascade

X-ray Irradiation activates immune response in human T-lymphocytes by eliciting a Ca²⁺signaling cascade

Recruitment Kinetics of DNA Repair Proteins Mdc1 and Rad52 but Not 53BP1 Depend on Damage Complexity

Calcium‑sensing receptor promotes high glucose‑induced myocardial fibrosis via upregulation of the TGF‑β1/Smads pathway in cardiac fibroblasts

Contact Info

Product

Resources

About

The Absence of an Early Calcium Response to Heavy-Ion Radiation in Mammalian Cells

Cited by 13 publications

References 33 publications

X-ray Irradiation activates immune response in human T-lymphocytes by eliciting a Ca2+signaling cascade

X-ray Irradiation activates immune response in human T-lymphocytes by eliciting a Ca2+signaling cascade

Recruitment Kinetics of DNA Repair Proteins Mdc1 and Rad52 but Not 53BP1 Depend on Damage Complexity

Calcium‑sensing receptor promotes high glucose‑induced myocardial fibrosis via upregulation of the TGF‑β1/Smads pathway in cardiac fibroblasts

Contact Info

Product

Resources

About

X-ray Irradiation activates immune response in human T-lymphocytes by eliciting a Ca²⁺signaling cascade

X-ray Irradiation activates immune response in human T-lymphocytes by eliciting a Ca²⁺signaling cascade