Summary of Study ST001866

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 PR001178. The data can be accessed directly via it's Project DOI: 10.21228/M8F99F This work is supported by NIH grant, U2C- DK119886.

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Study ID	ST001866
Study Title	Systemic metabolite changes due to PHD inhibition
Study Type	Comparative metabolomic analysis of serum metabolites detected by untargeted LC/MS and GC/MS platform
Study Summary	Prolonged cellular hypoxia leads to energetic failure and death. However, sublethal hypoxia can trigger an adaptive response called hypoxic preconditioning. While prolyl-hydroxylase (PHD) enzymes and hypoxia inducible factors (HIFs) have been identified as key elements of oxygen sensing machinery, the mechanisms by which hypoxic preconditioning protects against insults remain unclear. Here, we perform serum metabolomic profiling to assess alterations induced by hypoxic preconditioning. We discover that hypoxic preconditioning increases serum kynurenine levels and enhance kynurenine biotransformation leading to preservation of NAD+ in the post-ischemic kidney. Furthermore, we show that Indoleamine 2,3-dioxygenase 1 (Ido1) deficiency abolishes the systemic increase of kynurenine and the subsequent renoprotection generated by hypoxic preconditioning. Importantly, exogenous administration of kynurenine restores the hypoxic preconditioning in the context of Ido1 deficiency. Collectively, our findings demonstrate a critical role of Ido1/kynurenine axis in mediating hypoxic preconditioning
Institute	Northwestern University
Department	Medicine/Nephrology
Laboratory	Kapitsinou
Last Name	Kapitsinou
First Name	Pinelopi
Address	303 East Superior Street
Email	pinelopi.kapitsinou@northwestern.edu
Phone	312-503-8710
Submit Date	2021-07-03
Num Groups	2
Total Subjects	14
Num Males	14
Study Comments	N/A
Publications	Accepted in Cell Reports
Chear Study	No
Analysis Type Detail	LC-MS
Release Date	2022-01-02
Release Version	1

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Sample Preparation:

Sampleprep ID:	SP001949
Sampleprep Summary:	The metabolomic screening was conducted by Metabolon, Inc (Durham, NC). The sample preparation process was carried out using the automated MicroLab STAR® system from Hamilton Company. Sample preparation was conducted using a proprietary series of organic and aqueous extractions to remove the protein fraction while allowing maximum recovery of small molecules. The resulting extract was divided into two fractions; one for analysis by LC and one for analysis by GC. Samples were placed briefly on a TurboVap® (Zymark) to remove the organic solvent. Each sample was then frozen and dried under vacuum. Samples were then prepared for the appropriate instrument, either LC/MS or GC/MS.

Sampleprep ID:

SP001949

Sampleprep Summary:

The metabolomic screening was conducted by Metabolon, Inc (Durham, NC). The sample preparation process was carried out using the automated MicroLab STAR® system from Hamilton Company. Sample preparation was conducted using a proprietary series of organic and aqueous extractions to remove the protein fraction while allowing maximum recovery of small molecules. The resulting extract was divided into two fractions; one for analysis by LC and one for analysis by GC. Samples were placed briefly on a TurboVap® (Zymark) to remove the organic solvent. Each sample was then frozen and dried under vacuum. Samples were then prepared for the appropriate instrument, either LC/MS or GC/MS.