Delayed Cardiomyocyte Response to Total Body Particle Radiation Exposure - Identification of Regulatory Gene Network
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ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Matthew Coleman
PROVIDER: E-GEOD-68876 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:We examined molecular responses using transcriptome profiling in isolated left ventricular murine cardiomyocytes to 90 cGy, 1 GeV proton (1H) and 15 cGy, 1 GeV/nucleon (n) proton (56Fe) particles 1, 3, 7, 14 and 28 days after exposure. Unsupervised clustering analysis of gene expression segregated samples according to the radiation (IR) response, and time after exposure with 56Fe-IR showing the greatest level of gene modulation. 1H-IR exposures showed little differential transcript modulation. Network analysis categorized the major differentially expressed genes into cell cycle, oxidative responses and transcriptional regulation functional groups. Transcriptional networks identified key nodes regulating expression. Individual transcription factors were inferred to be active at 1, 3, 7, 14 and 28 days after exposure. Validation of the signal transduction network by protein analysis showed that particle IR clearly regulates a long lived signaling mechanism for p38 MAPK signaling and NFATc4 activation. Electrophoresis mobility shift assays supported the role of additional key transcription factors GATA-4, STAT-3 and NF-κB as regulators of the response at specific time points. These data suggest that the molecular response to 56Fe-IR is unique and shows long-lasting gene expression in cardiomyocytes, up to 28 days after exposure. Additionally, proteins involved in signal transduction and transcriptional activation via DNA binding play a role in the response to high charge (Z) and energy (E) particles (HZE). Our study may have implications for NASAâs efforts to develop heart disease risk estimates for astronauts safety via identification of specific HZE-IR molecular markers and for patients receiving conventional and particle radiotherapy. Transcriptome profiling in isolated left ventricular murine cardiomyocytes to 90 cGy, 1 GeV proton (1H) and 15 cGy, 1 GeV/nucleon (n) proton (56Fe) particles 1, 3, 7, 14 and 28 days after exposure.
2016-07-03 | E-GEOD-68875 | biostudies-arrayexpress
Project description:We examined molecular responses using transcriptome profiling in isolated left ventricular murine cardiomyocytes to 90 cGy, 1 GeV proton (1H) and 15 cGy, 1 GeV/nucleon (n) iron (56Fe) particles 1, 3, 7, 14 and 28 days after exposure. Unsupervised clustering analysis of gene expression segregated samples according to the radiation (IR) response, and time after exposure with 56Fe-IR showing the greatest level of gene modulation. 1H-IR exposures showed little differential transcript modulation. Network analysis categorized the major differentially expressed genes into cell cycle, oxidative responses and transcriptional regulation functional groups. Transcriptional networks identified key nodes regulating expression. Individual transcription factors were inferred to be active at 1, 3, 7, 14 and 28 days after exposure. Validation of the signal transduction network by protein analysis showed that particle IR clearly regulates a long lived signaling mechanism for p38 MAPK signaling and NFATc4 activation. Electrophoresis mobility shift assays supported the role of additional key transcription factors GATA-4, STAT-3 and NF-κB as regulators of the response at specific time points. These data suggest that the molecular response to 56Fe-IR is unique and shows long-lasting gene expression in cardiomyocytes, up to 28 days after exposure. Additionally, proteins involved in signal transduction and transcriptional activation via DNA binding play a role in the response to high charge (Z) and energy (E) particles (HZE). Our study may have implications for NASAâ??s efforts to develop heart disease risk estimates for astronauts safety via identification of specific HZE-IR molecular markers and for patients receiving conventional and particle radiotherapy. Transcriptome profiling in isolated left ventricular murine cardiomyocytes to 90 cGy, 1 GeV proton (1H) and 15 cGy, 1 GeV/nucleon (n) iron (56Fe) particles 1, 3, 7, 14 and 28 days after exposure.
2016-07-03 | E-GEOD-68874 | biostudies-arrayexpress
Project description:In recent years there is a growing epidemiological indication of excess risk of cardiovascular disease at low doses of ionizing radiation without a clear-cut threshold. It is proposed that damage to the vascular endothelium is critical in radiation-related cardiovascular diseases. In order to identify and better understand the underlying molecular mechanisms of high LET (Fe ions) and low LET (X-ray) radiation on endothelial cells, we performed a microarray analysis on immortalized human coronary artery endothelial cells irradiated with 2.00 Gy and compared them with sham-irradiated samples. RNA was extracted at different time points after irradiation (1 day, 7 days).
2017-10-02 | E-MTAB-5754 | biostudies-arrayexpress
Project description:Under certain circumstances, humans can be exposed to ionizing radiation from heavy ions. Examples are cancer patients undergoing particle therapy (e.g. carbon ions) or astronauts in deep Space missions (iron ions which contribute for a large fraction to the possible health effects of cosmic radiation because of their high ionisation power). Understanding the differences in the cellular response to low- and high-LET radiation is important in order to adequately model risk estimates based on extrapolations from low-LET exposures. To address this need, we compared the transcriptional profiles of freshly isolated peripheral blood mononuclear cells after exposure to 1 Gy of X-rays, iron ions or carbon ions. Data of X-ray exposure have been submitted in E-MTAB-3463: https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-3463/.
2018-02-21 | E-MTAB-5761 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE16518: Response of human lymphoblastoid cells to HZE (iron ions) or gamma-rays GSE16519: Response of human lymphoblastoid cells to activated medium Refer to individual Series
2011-04-01 | E-GEOD-16525 | biostudies-arrayexpress
Project description:Recently, stereotactic ablative radiotherapy (SABR) is adopted to noninvasively treat catheter ablation-refractory ventricular tachycardia (VT). VT episodes were dramatically reduced after SABR within few weeks, but underlying mechanisms of these clinical effects as well as potential mediator of early antiarrhythmic effects were unknown
2022-08-12 | PXD030878 | Pride
Project description:Transcriptional profiling of human lymphoblastoid TK6 cells comparing mock irradiated cells with cells exposed 24 hours previously to 1.67 Gy HZE (1 GeV/amu iron ions accelerated at the NASA Space Research Laboratory (NSRL) of Brookhaven National Laboratory) or 2.5 Gy 137Cs gamma rays. TK6 cells were mock irradiated or exposed to HZE or gamma-rays, and RNA was harvested 24 hours later. 3 biological replicates were independently grown and harvested during three different runs at the NSRL. One replicate per array.
2011-04-01 | E-GEOD-16518 | biostudies-arrayexpress
Project description:Transcriptional profiling of human lymphoblastoid TK6 cells comparing mock irradiaed cells resuspended in fresh untreated RPMI 1640 medium with cells resuspended in medium activated by exposure to 2.5 Gy HZE (1 GeV/amu iron ions accelerated at the NASA Space Research Laboratory (NSRL) of Brookhaven National Laboratory). Two-condition experiment, mock irradiated vs. cells exposed to activated medium. 3 biological replicates were independently grown and harvested during three different runs at the NSRL. One replicate per array.
2011-04-01 | E-GEOD-16519 | biostudies-arrayexpress
Project description:Plants exhibit a robust transcriptional response to gamma radiation which includes the induction of transcripts required for homologous recombination and the suppression of transcripts that promote cell cycle progression. Various DNA damaging agents induce different spectra of DNA damage as well as M-bM-^@M-^\collateralM-bM-^@M-^] damage to other cellular components and therefore are not expected to provoke identical responses by the cell. Here we study the effects of two different types of ionizing radiation (IR) treatment, HZE (1 GeV Fe26+ high mass, high charge, and high energy relativistic particles) and gamma photons, on the transcriptome of Arabidopsis thaliana seedlings. Both types of IR induce small clusters of radicals that can result in the formation of double strand breaks (DSBs), but HZE also produces linear arrays of extremely clustered damage. We performed these experiments across a range of time points (1.5-24 h after irradiation) in both wild-type plants and in mutants defective in the DSB-sensing protein kinase ATM. The two types of IR exhibit a shared double strand break-repair-related damage response, although they differ slightly in the timing, degree, and ATM-dependence of the response. The ATM-dependent, DNA metabolism-related transcripts of the M-bM-^@M-^\DSB responseM-bM-^@M-^] were also induced by other DNA damaging agents, but were not induced by conventional stresses. Both Gamma and HZE irradiation induced, at 24 h post-irradiation, ATM-dependent transcripts associated with a variety of conventional stresses; these were overrepresented for pathogen response, rather than DNA metabolism. In contrast, only HZE-irradiated plants, at 1.5 h after irradiation, exhibited an additional and very extensive transcriptional response, shared with plants experiencing M-bM-^@M-^\extended night.M-bM-^@M-^] This response was not apparent in gamma-irradiated plants. We treated 5-day-old WT and atm-1 seedlings of Arabidopsis thaliana with 100 Gy of Gamma radiation (over a span of 15 minutes) or 30 Gy of HZE (over a span of approximately 12 minutes). Gamma irradiations were completed at 8:40 am, while HZE irradiations were conducted in two runs (due to space limitations) which were completed at 1:09 and 1:28pm respectively. Gamma treated seedlings were sampled at 10:10 am, 11:40 am, 2:55 pm, 8:40 pm, and 8:40 am. HZE treated seedlings were sampled at 2:39 pm, 4:09 pm, 7:24 pm, 1:09 am, and 1:09 pm. Un-irradiated WT and atm-1 control seedlings were sampled at 10:45 am on Day #1 and 9:15 am on Day #2. There are a total of 22 experimental or control conditions, with two replicates per condition, yielding 44 samples overall.
2014-09-18 | E-GEOD-61484 | biostudies-arrayexpress
Project description:Background and Purpose: Cardiotoxicity is a well-known adverse effect of radiation therapy. Measurable abnormalities in the heart function indicate advanced and often irreversible heart damage. Therefore, early detection of cardiac toxicity is necessary to delay and alleviate the development of the disease. The present study investigated long-term serum proteome alterations following local heart irradiation using a mouse model with the aim to detect biomarkers of radiation-induced cardiac toxicity. Materials and Methods: Serum samples from C57BL/6J mice were collected 20 weeks after local heart irradiation with 8 Gy or 16 Gy X-ray; the controls were sham-irradiated. The samples were analyzed by quantitative proteomics based on data-independent acquisition mass spectrometry. The proteomics data were further investigated using bioinformatics and ELISA. Results: The analysis showed radiation-induced changes in the level of several serum proteins involved in the acute phase response, inflammation and cholesterol metabolism. We found significantly enhanced expression of pro-inflammatory cytokines (TNF-, TGF-, IL-1 and IL-6) in the serum of the irradiated mice. The level of free fatty acids, total cholesterol, low density lipoprotein (LDL) and oxidized LDL was increased whereas that of high density lipoprotein was decreased by irradiation. Conclusions: This study provides information on systemic effects of heart irradiation. It elucidates a radiation fingerprint in the serum that may be used to elucidate adverse cardiac effects after radiation therapy.
2021-09-10 | PXD024446 | Pride