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 IDST001866
Study TitleSystemic metabolite changes due to PHD inhibition
Study TypeComparative metabolomic analysis of serum metabolites detected by untargeted LC/MS and GC/MS platform
Study SummaryProlonged 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
DepartmentMedicine/Nephrology
LaboratoryKapitsinou
Last NameKapitsinou
First NamePinelopi
Address303 East Superior Street
Emailpinelopi.kapitsinou@northwestern.edu
Phone312-503-8710
Submit Date2021-07-03
Num Groups2
Total Subjects14
Num Males14
Study CommentsN/A
PublicationsAccepted in Cell Reports
Chear StudyNo
Analysis Type DetailLC-MS
Release Date2022-01-02
Release Version1
Pinelopi Kapitsinou Pinelopi Kapitsinou
https://dx.doi.org/10.21228/M8F99F
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Factors:

Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id local_sample_id Treatment
SA174494PHI_7PHI
SA174495PHI_1PHI
SA174496PHI_5PHI
SA174497PHI_6PHI
SA174498PHI_2PHI
SA174499PHI_3PHI
SA174500PHI_4PHI
SA174501Veh_11Vehicle
SA174502Veh_12Vehicle
SA174503Veh_10Vehicle
SA174504Veh_6Vehicle
SA174505Veh_7Vehicle
SA174506Veh_8Vehicle
SA174507Veh_9Vehicle
Showing results 1 to 14 of 14
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