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.

Show all samples | Perform analysis on untargeted data
Download mwTab file (text) | Download mwTab file(JSON) | Download data files

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
Email	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:

Treatment:

Treatment ID:	TR001206
Treatment Summary:	All experimental procedures involving live animals were conducted in accordance with the guidelines of the NIH Guide for the Care and Use of Laboratory Animals and approved by the Cleveland Clinic institutional animal care and use committee (IACUC, protocol #2016-1677). Wild type C57BL/6J mice were supplied by the Jackson Laboratory (Bar Harbor, ME). OIR model was based on the previously described procedure developed by LE Smith(Smith et al, 1994) and was described in detail elsewhere(Hoppe et al, 2014b; Sears et al, 2008; Singh et al, 2018). Metabolomics experiment was performed on p10 old OIR model mice Smith LE, Wesolowski E, McLellan A, Kostyk SK, D'Amato R, Sullivan R, D'Amore PA (1994) Oxygen-induced retinopathy in the mouse. Investigative ophthalmology & visual science 35: 101-111 Sears JE, Hoppe G, Ebrahem Q, Anand-Apte B (2008) Prolyl hydroxylase inhibition during hyperoxia prevents oxygen-induced retinopathy. Proceedings of the National Academy of Sciences 105: 19898-19903 Singh C, Sharma A, Hoppe G, Song W, Bolok Y, Sears JE (2018) 3-Hydroxypyruvate Destabilizes Hypoxia Inducible Factor and Induces Angiostasis. Investigative Ophthalmology & Visual Science 59: 3440-3448

Treatment ID:

TR001206

Treatment Summary:

All experimental procedures involving live animals were conducted in accordance with the guidelines of the NIH Guide for the Care and Use of Laboratory Animals and approved by the Cleveland Clinic institutional animal care and use committee (IACUC, protocol #2016-1677). Wild type C57BL/6J mice were supplied by the Jackson Laboratory (Bar Harbor, ME). OIR model was based on the previously described procedure developed by LE Smith(Smith et al, 1994) and was described in detail elsewhere(Hoppe et al, 2014b; Sears et al, 2008; Singh et al, 2018). Metabolomics experiment was performed on p10 old OIR model mice Smith LE, Wesolowski E, McLellan A, Kostyk SK, D'Amato R, Sullivan R, D'Amore PA (1994) Oxygen-induced retinopathy in the mouse. Investigative ophthalmology & visual science 35: 101-111 Sears JE, Hoppe G, Ebrahem Q, Anand-Apte B (2008) Prolyl hydroxylase inhibition during hyperoxia prevents oxygen-induced retinopathy. Proceedings of the National Academy of Sciences 105: 19898-19903 Singh C, Sharma A, Hoppe G, Song W, Bolok Y, Sears JE (2018) 3-Hydroxypyruvate Destabilizes Hypoxia Inducible Factor and Induces Angiostasis. Investigative Ophthalmology & Visual Science 59: 3440-3448