Summary of Study ST002032

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 IDST002032
Study TitleIrradiation causes alterations of polyamine, purine and sulfur metabolism in red blood cells and multiple organs (Blood plasma)
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
Address1635 Aurora Ct, Aurora, CO, 80045, USA
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:SU002114
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
SA19131449IV iron Gy10
SA19131550IV iron Gy10
SA19131647IV iron Gy10
SA19131748IV iron Gy10
SA19131846IV iron Gy10
SA19131957IV iron Gy11
SA19132058IV iron Gy11
SA19132156IV iron Gy11
SA19132259IV iron Gy11
SA19132360IV iron Gy11
SA19132419IV iron Gy7
SA19132520IV iron Gy7
SA19132618IV iron Gy7
SA19132717IV iron Gy7
SA19132816IV iron Gy7
SA19132928IV iron Gy8
SA19133029IV iron Gy8
SA19133130IV iron Gy8
SA19133226IV iron Gy8
SA19133327IV iron Gy8
SA19133437IV iron Gy9
SA19133539IV iron Gy9
SA19133640IV iron Gy9
SA19133736IV iron Gy9
SA19133838IV iron Gy9
SA1913396IV iron no irradiated
SA1913407IV iron no irradiated
SA1913418IV iron no irradiated
SA19134210IV iron no irradiated
SA1913439IV iron no irradiated
SA19134441Saline Gy10
SA19134544Saline Gy10
SA19134645Saline Gy10
SA19134743Saline Gy10
SA19134842Saline Gy10
SA19134951Saline Gy11
SA19135053Saline Gy11
SA19135154Saline Gy11
SA19135255Saline Gy11
SA19135352Saline Gy11
SA19135415Saline Gy7
SA19135514Saline Gy7
SA19135613Saline Gy7
SA19135711Saline Gy7
SA19135825Saline Gy8
SA19135922Saline Gy8
SA19136024Saline Gy8
SA19136123Saline Gy8
SA19136221Saline Gy8
SA19136332Saline Gy9
SA19136431Saline Gy9
SA19136535Saline Gy9
SA19136633Saline Gy9
SA19136734Saline Gy9
SA1913682Saline no irradiated
SA1913693Saline no irradiated
SA1913701Saline no irradiated
SA1913714Saline no irradiated
Showing results 1 to 58 of 58

Collection:

Collection ID:CO002107
Collection Summary:At day +4 post irradiation, mice were euthanized and blood was collected by cardiac puncture in heparinized syringe. Plasma obtained after centrifugation at 4500 g for 10 minutes at +4°C
Sample Type:Blood (plasma)

Treatment:

Treatment ID:TR002126
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:SP002120
Sampleprep Summary:A volume of 50μl of frozen plasma was extracted in 450μl 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 AN003303 AN003304
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:CH002442
Instrument Name:Thermo Vanquish
Column Name:Phenomenex Kinetex C18 (150 x 2.1mm, 2.6 um)
Chromatography Type:Reversed phase
  
Chromatography ID:CH002443
Instrument Name:Thermo Vanquish
Column Name:Phenomenex Kinetex C18 (150 x 2.1mm, 2.6 um)
Chromatography Type:Reversed phase

MS:

MS ID:MS003073
Analysis ID:AN003303
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. 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:MS003074
Analysis ID:AN003304
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. 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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