Delayed Cardiomyocyte Response to Total Body Particle Radiation Exposure - Identification of Regulatory Gene Network
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PROVIDER: PRJNA283959 | ENA |
REPOSITORIES: ENA
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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: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 NASA’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.
2016-01-01 | GSE68875 | GEO
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 NASA’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.
2016-01-01 | GSE68874 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2016-07-03 | E-GEOD-68876 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below.
2016-01-01 | GSE68876 | GEO
Project description:The purpose of this study was to identify genes that are modulated by alpha particle radiation Cell types were independently exposed to alpha particle radiation using Americium-241 discs (0.9Gy/hr) at a dose range from 0-1.5 Gy. Twenty-four hours post-exposure cells were harvested and RNA was extracted and subjected to microarray analysis.
2016-04-22 | GSE80547 | GEO
Project description:To date, there have been limited high quality libraries of cardiomyocyte maturation during the perinatal period, in part owing to the difficulty of isolating large perinatal cardiomyocytes. We previously developed a method utilizing large-particle fluorescent activated cell sorting (LP-FACS) to isolate adult cardiomyocytes for single cell RNA-seq (Kannan et al., Circ Res, 2019). We utilize this method to generate a reference of perinatal cardiomyocyte maturation.
2020-04-01 | GSE147807 | GEO
Project description:Four human-derived cell types: transformed monocytes (THP-1), transformed lung epithelial cells (A549), normal human pulmonary endothelial cells (HPEAC) and normal lung fibroblasts (HFL-1) Cell types were independently exposed to alpha particle radiation using Americium-241 discs (0.9Gy/hr) at a dose range from 0-1.5 Gy. Twenty-four hours post-exposure cells were harvested and RNA was extracted and subjected to microarray analysis.
2016-05-04 | GSE81067 | GEO
Project description:The population's increasing risk of acute large-scale radiological/nuclear exposures underlines the need for functional radiation biomarkers. As ionizing radiation triggers a complex response on the genome, proteome, and metabolome level, all were already reported as suitable indicators of radiation-induced damage in vitro or in animal models. We aim to analyze the blood of total-body irradiated (TBI) leukaemia patients using a mass spectrometry approach and to identify and quantify plasma proteins before and after irradiation. Combining two independent mass spectrometry approaches we identified 15 plasma proteins differing in the blood of TBI patients before and after irradiation. The majority of proteins were associated with the inflammatory responce of the immune system and with metabolism of lipids. These candidate radiation biomarkers might have implications for practical biological dosimetry.
2024-06-16 | PXD043516 | Pride