Unknown,Transcriptomics,Genomics,Proteomics

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Effect of 90Sr internal emitter on gene expression in mouse blood

ABSTRACT: Background The radioactive isotope Strontium-90 (90Sr) may be released as a component of fallout from nuclear accidents, or in the event of a radiological incident such as detonation of an improvised nuclear device, and if ingested poses a significant health risk to exposed individuals. In order to better understand the response to 90Sr, using an easily attainable and standard biodosimetry sample fluid, we analyzed the global transcriptomic response of blood cells in an in vivo model system. Methods We injected C57BL/6 mice with a solution of 90SrCl2 and followed them over a 30-day period. At days 4, 7, 9, 25 and 30, we collected blood and isolated RNA for microarray analyses. These days corresponded to target doses in a range from 1 to 5 Gy. We investigated changes in mRNA levels using microarrays, and changes in specific microRNA (miRNA) predicted to be involved in the response using qRT-PCR. Results We identified 8082 differentially expressed genes in the blood of mice exposed to 90Sr compared with controls. Common biological functions were affected throughout the study, including apoptosis of B and T lymphocytes, and atrophy of lymphoid organs. Cellular functions such as RNA degradation and lipid metabolism were also affected during the study. The broad down regulation of genes observed in our study suggested a potential role for miRNA in gene regulation. We tested candidate miRNAs, mmu-miR-16, mmu-miR-124, mmu-miR-125 and mmu-mir-21; and found that all were induced at the earliest time point, day 4. Conclusions Our study is the first to report the transcriptomic response of blood cells to the internal emitter 90Sr in mouse and a possible role for microRNA in gene regulation after 90Sr exposure. The most dramatic effect was observed on gene expression related to B-cell development and RNA maintenance. These functions were affected by genes that were down regulated throughout the study, suggesting severely compromised antigen response, which may be a result of the deposition of the radioisotope proximal to the hematopoietic compartment in bone. Radiation induced gene expression in mouse blood was measured at 4, 7, 9, 25 and 30 days after 90Sr injection. Six independent experiments were performed at each time point.

ORGANISM(S): Mus musculus

SUBMITTER: Shanaz Ghandhi

PROVIDER: E-GEOD-64775 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Background The radioactive isotope Strontium-90 (90Sr) may be released as a component of fallout from nuclear accidents, or in the event of a radiological incident such as detonation of an improvised nuclear device, and if ingested poses a significant health risk to exposed individuals. In order to better understand the response to 90Sr, using an easily attainable and standard biodosimetry sample fluid, we analyzed the global transcriptomic response of blood cells in an in vivo model system. Methods We injected C57BL/6 mice with a solution of 90SrCl2 and followed them over a 30-day period. At days 4, 7, 9, 25 and 30, we collected blood and isolated RNA for microarray analyses. These days corresponded to target doses in a range from 1 to 5 Gy. We investigated changes in mRNA levels using microarrays, and changes in specific microRNA (miRNA) predicted to be involved in the response using qRT-PCR. Results We identified 8082 differentially expressed genes in the blood of mice exposed to 90Sr compared with controls. Common biological functions were affected throughout the study, including apoptosis of B and T lymphocytes, and atrophy of lymphoid organs. Cellular functions such as RNA degradation and lipid metabolism were also affected during the study. The broad down regulation of genes observed in our study suggested a potential role for miRNA in gene regulation. We tested candidate miRNAs, mmu-miR-16, mmu-miR-124, mmu-miR-125 and mmu-mir-21; and found that all were induced at the earliest time point, day 4. Conclusions Our study is the first to report the transcriptomic response of blood cells to the internal emitter 90Sr in mouse and a possible role for microRNA in gene regulation after 90Sr exposure. The most dramatic effect was observed on gene expression related to B-cell development and RNA maintenance. These functions were affected by genes that were down regulated throughout the study, suggesting severely compromised antigen response, which may be a result of the deposition of the radioisotope proximal to the hematopoietic compartment in bone.

Project description:MiRNAs are essential mediators of many biological processes. The aim of this study was to investigate the dynamics of miRNA-mRNA regulatory networks during exercise and subsequent recovery period. Here we monitored the transcriptome changes by microarray analysis of the whole blood of eight highly trained athletes after 30 min of moderate exercise followed by 30 min and 60 min of recovery period. We combined expression profiling and bioinformatics and analysed metabolic pathways enriched with differentially expressed mRNAs and then mRNAs which are known to be validated targets of differentially expressed miRNAs. Finally we revealed four dynamically regulated networks comprising differentially expressed miRNAs and their known target mRNAs with anti-correlated expression profiles over time. The data suggest that hsa-miR-21-5p regulated TGFBR3, PDGFD and PPM1L mRNAs. Hsa-miR-24-2-5p was likely to be responsible for MYC and KCNJ2 genes and hsa-miR-27a-5p for ST3GAL6. The targets of hsa-miR-181a-5p included ROPN1L and SLC37A3. All these mRNAs are involved in processes highly relevant to exercise response, including immune function, apoptosis, membrane traffic of proteins and transcription regulation. We have identified four miRNA-mRNA networks dynamically regulated following exercise. This work is the first study to monitor miRNAs and mRNAs in parallel into recovery period. The results provide a novel insight into the regulatory role of miRNAs in stress adaptation. Each subject performed a treadmill test with an incremental step protocol until exhaustion. Blood samples were taken from the antecubital vein using indwelling catheter before (T1), immediately after ramp test to exaustion (T2) and after 30 min of recovery (T3). Two weeks later, athletes participated in the main exercise, consisting of running at 80% VO2 peak for 30 min on a treadmill. Blood samples were taken from the antecubital vein using indwelling catheter before (T4), immediately after running at 80% VO2 peak for 30 min on a treadmill (T5), after 30 min (T6) and 60 min (T7) of recovery.

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Effect of 90Sr internal emitter on gene expression in mouse blood

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