Summary of Study ST002039

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 IDST002039
Study TitleIrradiation causes alterations of polyamine, purine and sulfur metabolism in red blood cells and multiple organs (Brain)
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 Date2021-12-28
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:SU002121
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
SA19171949IV iron Gy10
SA19172050IV iron Gy10
SA19172147IV iron Gy10
SA19172248IV iron Gy10
SA19172346IV iron Gy10
SA19172457IV iron Gy11
SA19172558IV iron Gy11
SA19172656IV iron Gy11
SA19172759IV iron Gy11
SA19172860IV iron Gy11
SA19172919IV iron Gy7
SA19173020IV iron Gy7
SA19173118IV iron Gy7
SA19173217IV iron Gy7
SA19173316IV iron Gy7
SA19173428IV iron Gy8
SA19173529IV iron Gy8
SA19173630IV iron Gy8
SA19173726IV iron Gy8
SA19173827IV iron Gy8
SA19173937IV iron Gy9
SA19174039IV iron Gy9
SA19174140IV iron Gy9
SA19174236IV iron Gy9
SA19174338IV iron Gy9
SA1917446IV iron no irradiated
SA1917457IV iron no irradiated
SA1917468IV iron no irradiated
SA19174710IV iron no irradiated
SA1917489IV iron no irradiated
SA19174941Saline Gy10
SA19175044Saline Gy10
SA19175145Saline Gy10
SA19175243Saline Gy10
SA19175342Saline Gy10
SA19175451Saline Gy11
SA19175553Saline Gy11
SA19175654Saline Gy11
SA19175755Saline Gy11
SA19175852Saline Gy11
SA19175915Saline Gy7
SA19176014Saline Gy7
SA19176113Saline Gy7
SA19176211Saline Gy7
SA19176325Saline Gy8
SA19176422Saline Gy8
SA19176524Saline Gy8
SA19176623Saline Gy8
SA19176721Saline Gy8
SA19176832Saline Gy9
SA19176931Saline Gy9
SA19177035Saline Gy9
SA19177133Saline Gy9
SA19177234Saline Gy9
SA1917732Saline no irradiated
SA1917743Saline no irradiated
SA1917751Saline no irradiated
SA1917764Saline no irradiated
Showing results 1 to 58 of 58

Collection:

Collection ID:CO002114
Collection Summary:At day +4 post irradiation, mice were euthanized and tissue was collected, weighted, and stored at -80C until further processing.
Sample Type:Brain

Treatment:

Treatment ID:TR002133
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:SP002127
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 AN003317 AN003318
Analysis type MS MS
Chromatography type Reversed phase Reversed phase
Chromatography system Thermo Vanquish Thermo Vanquish
Column Phenomenex Kinetex C18 (150 x 2.1mm,2.6um) Phenomenex Kinetex C18 (150 x 2.1mm,2.6um)
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:CH002456
Instrument Name:Thermo Vanquish
Column Name:Phenomenex Kinetex C18 (150 x 2.1mm,2.6um)
Chromatography Type:Reversed phase
  
Chromatography ID:CH002457
Instrument Name:Thermo Vanquish
Column Name:Phenomenex Kinetex C18 (150 x 2.1mm,2.6um)
Chromatography Type:Reversed phase

MS:

MS ID:MS003087
Analysis ID:AN003317
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:MS003088
Analysis ID:AN003318
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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