Summary of Study ST001130
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 PR000755. The data can be accessed directly via it's Project DOI: 10.21228/M8367J 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 | ST001130 |
| Study Title | Urea cycle and 1C/serine metabolism in the prevention of oxygen induced retinopathy |
| Study Summary | Untargeted metabolite profiling links the urea cycle and 1C/serine metabolism in the prevention of oxygen induced retinopathy by hepatic HIF stabilization. Premature infants require oxygen supplementation to survive that is simultaneously toxic to developing tissues. We have demonstrated that hypoxia inducible factor (HIF) stabilization during hyperoxia prevents oxygen induced retinopathy (OIR) and lung disease. Here, untargeted metabolite profiling coupled to XCMS systems biology analysis finds that serine/1C and urea cycles dominate pathway enrichment graphs. MS1 peak areas and MS2 library matches reveal 50% or more increased levels of plasma and retina serine, glycine, hypotaurine, methionine, and taurine. In addition, N-acetylglutamate increased 4-fold in serum, while orotate, citrulline, arginine, aspartate, glutamine were at least 50% increased after HIF stabilization. Targeted data analysis in vivo finds that retinal serine and glycine were derived from liver. HIF-1α2lox/2lox; albumin-cre KO had reduced levels of serine and retinal glycine. Inhibition of 1C metabolism blocked rescue by HIF stabilization. The metabolic phenotype of mice protected from OIR by HIF stabilization is dependent on hepatic serine/1C metabolism and urea cycle. |
| Institute | Cole Eye Institute |
| Department | Cleveland Clinic |
| Last Name | Singh |
| First Name | Charandeep |
| Address | 9500 Euclid Avenue |
| cxs065@gmail.com | |
| Phone | (216) 444-8232 |
| Submit Date | 2019-01-31 |
| Analysis Type Detail | LC-MS |
| Release Date | 2020-06-20 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Combined analysis:
| Analysis ID | AN001855 |
|---|---|
| Analysis type | MS |
| Chromatography type | HILIC |
| Chromatography system | Thermo Vanquish |
| Column | SeQuant ZIC-HILIC (100 x 2.1mm,3.5um) |
| MS Type | ESI |
| MS instrument type | Orbitrap |
| MS instrument name | Thermo Q Exactive HF hybrid Orbitrap |
| Ion Mode | POSITIVE |
| Units | Area under the curve Arbitrary units |
Chromatography:
| Chromatography ID: | CH001342 |
| Chromatography Summary: | Chromatographic separation was performed on SeQuant ZIC-HILIC column with dimensions 150 x 2.1 mm, 3.5 µm, 100 Å (Merck, Darmstadt, Germany) attached to a precolumn SeQuant ZIC-HILIC with dimensions 20 x 2.1 mm, 3.5 µm, 100 Å (Merck, Darmstadt, Germany). The LC method used for separation of metabolites using the ZIC-HILIC column was adapted from Singh et al. al.(Singh et al, 2017). Briefly, gradient of solvent A (0.1% formic acid in water) and solvent B (0.08% formic acid in ACN) ramped from 80% B to 35% B in 23 minutes, followed by a wash step with 5% B from 25-30 min and then re-equilibration with 80% B from 25-30 min. Column oven was set to 20⁰C and a constant flow of solvents was set to 150 µl min-1. Samples were kept on 4⁰C auto-sampler throughout the measurements and 10 μl (plasma) of sample was injected. Singh C, Glaab E, Linster CL (2017) Molecular Identification of d-Ribulokinase in Budding Yeast and Mammals. The Journal of biological chemistry 292: 1005-1028 |
| Instrument Name: | Thermo Vanquish |
| Column Name: | SeQuant ZIC-HILIC (100 x 2.1mm,3.5um) |
| Column Temperature: | 20 |
| Flow Gradient: | ramped from 80% B to 35% B in 23 minutes, followed by a wash step with 5% B from 25-30 min and then re-equilibration with 80% B from 25-30 min. |
| Flow Rate: | 150 µl/min |
| Solvent A: | 100% water; 0.1% formic acid |
| Solvent B: | 100% acetonitrile; 0.08% formic acid |
| Chromatography Type: | HILIC |
