Summary of Study ST002035

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001288. The data can be accessed directly via it's Project DOI: 10.21228/M8771V This work is supported by NIH grant, U2C- DK119886.

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This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST002035
Study TitleIrradiation causes alterations of polyamine, purine and sulfur metabolism in red blood cells and multiple organs (Heart)
Study SummaryInvestigating the metabolic effects of radiation is critical to understand the impact of radiotherapy (e.g., for bone marrow irradiation prior to hematopoietic stem cell transplantation in the clinic or in laboratory studies), space travel, and exposure to environmental radiation. In patients undergoing hemopoietic stem cell transplantation, iron overload is a common risk factor for poor outcomes. Previous studies assert that both irradiation and iron independently modulate tryptophan and indole metabolism of the microbiome, which may in turn impact host immune response. However, no studies have interrogated the multi-organ effects of these treatments concurrently. Herein, we use a model that recapitulate transfusional iron overload, a condition often observed in chronically transfused patients with thalassemia, sickle cell disease, or myelodysplastic syndrome. We applied an omics approach to investigate the impact of both iron load and irradiation on the host metabolome. Our results revealed dose-dependent effects of irradiation in red blood cells (RBC), plasma, spleen, and liver energy and redox metabolism. Increases in polyamines and purine salvage metabolites were observed in organs with high oxygen consumption including the heart, kidney, and brain. Irradiation also impacted the metabolism of the duodenum, colon, and stool, suggesting a potential effect on the microbiome. Iron infusion affected the respose to radiation in the organs and blood, especially in RBC polyamine metabolism and spleen antioxidant metabolism, and affected glucose, sulfur (especially methionine and glutathione systems) and tryptophan metabolism in the liver, stool, and brain. Together, the results suggest that radiation impacts metabolism on a multi-organ level with a significant interaction of host iron status.
Institute
University of Colorado Anschutz Medical Campus
Last NameRoy
First NameMicaela
Address13001 E 17th Pl, Aurora, CO 80045
Emailmicaela.roy@cuanschutz.edu
Phone303-724-3339
Submit Date2021-12-27
Raw Data AvailableYes
Raw Data File Type(s)raw(Thermo)
Analysis Type DetailLC-MS
Release Date2022-01-21
Release Version1
Micaela Roy Micaela Roy
https://dx.doi.org/10.21228/M8771V
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:


Project:

Project ID:PR001288
Project DOI:doi: 10.21228/M8771V
Project Title:Irradiation causes alterations of polyamine, purine and sulfur metabolism in red blood cells and multiple organs
Project Summary:Investigating the metabolic effects of radiation is critical to understand the impact of radiotherapy (e.g., for bone marrow irradiation prior to hematopoietic stem cell transplantation in the clinic or in laboratory studies), space travel, and exposure to environmental radiation. In patients undergoing hemopoietic stem cell transplantation, iron overload is a common risk factor for poor outcomes. Previous studies assert that both irradiation and iron independently modulate tryptophan and indole metabolism of the microbiome, which may in turn impact host immune response. However, no studies have interrogated the multi-organ effects of these treatments concurrently. Herein, we use a model that recapitulate transfusional iron overload, a condition often observed in chronically transfused patients with thalassemia, sickle cell disease, or myelodysplastic syndrome. We applied an omics approach to investigate the impact of both iron load and irradiation on the host metabolome. Our results revealed dose-dependent effects of irradiation in red blood cells (RBC), plasma, spleen, and liver energy and redox metabolism. Increases in polyamines and purine salvage metabolites were observed in organs with high oxygen consumption including the heart, kidney, and brain. Irradiation also impacted the metabolism of the duodenum, colon, and stool, suggesting a potential effect on the microbiome. Iron infusion affected the respose to radiation in the organs and blood, especially in RBC polyamine metabolism and spleen antioxidant metabolism, and affected glucose, sulfur (especially methionine and glutathione systems) and tryptophan metabolism in the liver, stool, and brain. Together, the results suggest that radiation impacts metabolism on a multi-organ level with a significant interaction of host iron status.
Institute:University of Colorado Anschutz Medical Campus
Last Name:Roy
First Name:Micaela
Address:13001 E 17th Pl, Aurora
Email:micaela.roy@cuanschutz.edu
Phone:9259977554

Subject:

Subject ID:SU002117
Subject Type:Mammal
Subject Species:Mus musculus
Taxonomy ID:10090

Factors:

Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id local_sample_id Treatment Radiation Dose
SA19148749IV iron Gy10
SA19148850IV iron Gy10
SA19148947IV iron Gy10
SA19149048IV iron Gy10
SA19149146IV iron Gy10
SA19149257IV iron Gy11
SA19149358IV iron Gy11
SA19149456IV iron Gy11
SA19149559IV iron Gy11
SA19149660IV iron Gy11
SA19149719IV iron Gy7
SA19149820IV iron Gy7
SA19149918IV iron Gy7
SA19150017IV iron Gy7
SA19150116IV iron Gy7
SA19150228IV iron Gy8
SA19150329IV iron Gy8
SA19150430IV iron Gy8
SA19150526IV iron Gy8
SA19150627IV iron Gy8
SA19150737IV iron Gy9
SA19150839IV iron Gy9
SA19150940IV iron Gy9
SA19151036IV iron Gy9
SA19151138IV iron Gy9
SA1915126IV iron no irradiated
SA1915137IV iron no irradiated
SA1915148IV iron no irradiated
SA19151510IV iron no irradiated
SA1915169IV iron no irradiated
SA19151741Saline Gy10
SA19151844Saline Gy10
SA19151945Saline Gy10
SA19152043Saline Gy10
SA19152142Saline Gy10
SA19152251Saline Gy11
SA19152353Saline Gy11
SA19152454Saline Gy11
SA19152555Saline Gy11
SA19152652Saline Gy11
SA19152715Saline Gy7
SA19152814Saline Gy7
SA19152913Saline Gy7
SA19153011Saline Gy7
SA19153125Saline Gy8
SA19153222Saline Gy8
SA19153324Saline Gy8
SA19153423Saline Gy8
SA19153521Saline Gy8
SA19153632Saline Gy9
SA19153731Saline Gy9
SA19153835Saline Gy9
SA19153933Saline Gy9
SA19154034Saline Gy9
SA1915412Saline no irradiated
SA1915423Saline no irradiated
SA1915431Saline no irradiated
SA1915444Saline no irradiated
Showing results 1 to 58 of 58

Collection:

Collection ID:CO002110
Collection Summary:At day +4 post irradiation, mice were euthanized and tissue was collected, weighted, and stored at -80C until further processing.
Sample Type:Heart

Treatment:

Treatment ID:TR002129
Treatment Summary:After one week of acclimatization in a pathogen-free facility, cohorts of mice were retro-orbitally infused with phosphate buffer saline (PBS) or 12.5 mg of iron dextran (Henry Shein Animal Health, Dublin, OH), twice a week for 2 weeks for a total of 50 mg of iron. After 2 days of rest, mice were then divided in groups and irradiated with 7, 8, 9, 10, 11 Gy of C-137 (n=5 per group). Total dose was split in 2 doses 3 hours apart.

Sample Preparation:

Sampleprep ID:SP002123
Sampleprep Summary:Tissue was extracted in 1mL of methanol:acetonitrile:water (5:3:2, v/v/v).29 After vortexing at 4°C for 30 min, extracts were separated from the protein pellet by centrifugation for 10 min at 10,000g at 4°C and stored at −80°C until analysis.

Combined analysis:

Analysis ID AN003309 AN003310
Analysis type MS MS
Chromatography type Reversed phase Reversed phase
Chromatography system Thermo Vanquish Thermo Vanquish
Column Phenomenex Kinetex C18 (150 x 2.1mm, 2.6 um) Phenomenex Kinetex C18 (150 x 2.1mm, 2.6 um)
MS Type ESI ESI
MS instrument type Orbitrap Orbitrap
MS instrument name Thermo Q Exactive Orbitrap Thermo Q Exactive Orbitrap
Ion Mode POSITIVE NEGATIVE
Units peak area top peak area top

Chromatography:

Chromatography ID:CH002448
Instrument Name:Thermo Vanquish
Column Name:Phenomenex Kinetex C18 (150 x 2.1mm, 2.6 um)
Chromatography Type:Reversed phase
  
Chromatography ID:CH002449
Instrument Name:Thermo Vanquish
Column Name:Phenomenex Kinetex C18 (150 x 2.1mm, 2.6 um)
Chromatography Type:Reversed phase

MS:

MS ID:MS003079
Analysis ID:AN003309
Instrument Name:Thermo Q Exactive Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:Samples (10uL injection for cells, 20uL injection for SUPs) were introduced to the MS via electrospray ionization with the MS scanning in full MS mode (2 µscans) and ddMS2 (top15) over the range of 65-950 m/z. Technical replicates were injected every six to twelve samples to ensure instrument stability (Nemkov et al., 2019). Metabolites were manually selected integrated with Maven (Princeton University) in conjunction with the KEGG database. Peak quality was determined using blanks, technical mixes, and 13C abundance.
Ion Mode:POSITIVE
  
MS ID:MS003080
Analysis ID:AN003310
Instrument Name:Thermo Q Exactive Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:Samples (10uL injection for cells, 20uL injection for SUPs) were introduced to the MS via electrospray ionization with the MS scanning in full MS mode (2 µscans) and ddMS2 (top15) over the range of 65-950 m/z. Technical replicates were injected every six to twelve samples to ensure instrument stability (Nemkov et al., 2019). Metabolites were manually selected integrated with Maven (Princeton University) in conjunction with the KEGG database. Peak quality was determined using blanks, technical mixes, and 13C abundance.
Ion Mode:NEGATIVE
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