Summary of Study ST002040
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.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
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.
| Study ID | ST002040 |
| Study Title | Irradiation causes alterations of polyamine, purine and sulfur metabolism in red blood cells and multiple organs (Colon) |
| Study 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 | 1635 Aurora Ct, Aurora, CO, 80045, USA |
| micaela.roy@cuanschutz.edu | |
| Phone | 303-724-3339 |
| Submit Date | 2021-12-28 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | raw(Thermo) |
| Analysis Type Detail | LC-MS |
| Release Date | 2022-01-21 |
| Release Version | 1 |
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: | SU002122 |
| 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 | Condition |
|---|---|---|
| SA191777 | 49 | IV iron | Radiation Dose:Gy10 |
| SA191778 | 50 | IV iron | Radiation Dose:Gy10 |
| SA191779 | 47 | IV iron | Radiation Dose:Gy10 |
| SA191780 | 48 | IV iron | Radiation Dose:Gy10 |
| SA191781 | 46 | IV iron | Radiation Dose:Gy10 |
| SA191782 | 57 | IV iron | Radiation Dose:Gy11 |
| SA191783 | 58 | IV iron | Radiation Dose:Gy11 |
| SA191784 | 56 | IV iron | Radiation Dose:Gy11 |
| SA191785 | 59 | IV iron | Radiation Dose:Gy11 |
| SA191786 | 60 | IV iron | Radiation Dose:Gy11 |
| SA191787 | 19 | IV iron | Radiation Dose:Gy7 |
| SA191788 | 20 | IV iron | Radiation Dose:Gy7 |
| SA191789 | 18 | IV iron | Radiation Dose:Gy7 |
| SA191790 | 16 | IV iron | Radiation Dose:Gy7 |
| SA191791 | 17 | IV iron | Radiation Dose:Gy7 |
| SA191792 | 28 | IV iron | Radiation Dose:Gy8 |
| SA191793 | 26 | IV iron | Radiation Dose:Gy8 |
| SA191794 | 29 | IV iron | Radiation Dose:Gy8 |
| SA191795 | 27 | IV iron | Radiation Dose:Gy8 |
| SA191796 | 37 | IV iron | Radiation Dose:Gy9 |
| SA191797 | 39 | IV iron | Radiation Dose:Gy9 |
| SA191798 | 40 | IV iron | Radiation Dose:Gy9 |
| SA191799 | 36 | IV iron | Radiation Dose:Gy9 |
| SA191800 | 38 | IV iron | Radiation Dose:Gy9 |
| SA191801 | 6 | IV iron | Radiation Dose:no irradiated |
| SA191802 | 7 | IV iron | Radiation Dose:no irradiated |
| SA191803 | 8 | IV iron | Radiation Dose:no irradiated |
| SA191804 | 10 | IV iron | Radiation Dose:no irradiated |
| SA191805 | 9 | IV iron | Radiation Dose:no irradiated |
| SA191806 | 41 | Saline | Radiation Dose:Gy10 |
| SA191807 | 44 | Saline | Radiation Dose:Gy10 |
| SA191808 | 45 | Saline | Radiation Dose:Gy10 |
| SA191809 | 43 | Saline | Radiation Dose:Gy10 |
| SA191810 | 42 | Saline | Radiation Dose:Gy10 |
| SA191811 | 51 | Saline | Radiation Dose:Gy11 |
| SA191812 | 52 | Saline | Radiation Dose:Gy11 |
| SA191813 | 54 | Saline | Radiation Dose:Gy11 |
| SA191814 | 55 | Saline | Radiation Dose:Gy11 |
| SA191815 | 53 | Saline | Radiation Dose:Gy11 |
| SA191816 | 15 | Saline | Radiation Dose:Gy7 |
| SA191817 | 14 | Saline | Radiation Dose:Gy7 |
| SA191818 | 13 | Saline | Radiation Dose:Gy7 |
| SA191819 | 11 | Saline | Radiation Dose:Gy7 |
| SA191820 | 24 | Saline | Radiation Dose:Gy8 |
| SA191821 | 22 | Saline | Radiation Dose:Gy8 |
| SA191822 | 23 | Saline | Radiation Dose:Gy8 |
| SA191823 | 25 | Saline | Radiation Dose:Gy8 |
| SA191824 | 21 | Saline | Radiation Dose:Gy8 |
| SA191825 | 32 | Saline | Radiation Dose:Gy9 |
| SA191826 | 31 | Saline | Radiation Dose:Gy9 |
| SA191827 | 35 | Saline | Radiation Dose:Gy9 |
| SA191828 | 33 | Saline | Radiation Dose:Gy9 |
| SA191829 | 34 | Saline | Radiation Dose:Gy9 |
| SA191830 | 2 | Saline | Radiation Dose:no irradiated |
| SA191831 | 3 | Saline | Radiation Dose:no irradiated |
| SA191832 | 1 | Saline | Radiation Dose:no irradiated |
| SA191833 | 4 | Saline | Radiation Dose:no irradiated |
| Showing results 1 to 57 of 57 |
Collection:
| Collection ID: | CO002115 |
| Collection Summary: | At day +4 post irradiation, mice were euthanized and tissue was collected, weighted, and stored at -80C until further processing. |
| Sample Type: | Colon |
Treatment:
| Treatment ID: | TR002134 |
| 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: | SP002128 |
| 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 | AN003319 | AN003320 |
|---|---|---|
| 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: | CH002458 |
| Instrument Name: | Thermo Vanquish |
| Column Name: | Phenomenex Kinetex C18 (150 x 2.1mm,2.6um) |
| Chromatography Type: | Reversed phase |
| Chromatography ID: | CH002459 |
| Instrument Name: | Thermo Vanquish |
| Column Name: | Phenomenex Kinetex C18 (150 x 2.1mm,2.6um) |
| Chromatography Type: | Reversed phase |
MS:
| MS ID: | MS003089 |
| Analysis ID: | AN003319 |
| 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: | MS003090 |
| Analysis ID: | AN003320 |
| 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 |
