Tissue metabolic profiling shows that saccharopine accumulates during renal ischemic-reperfusion injury, while kynurenine and itaconate accumulate in renal allograft rejection.

TitleTissue metabolic profiling shows that saccharopine accumulates during renal ischemic-reperfusion injury, while kynurenine and itaconate accumulate in renal allograft rejection.
Publication TypeJournal Article
Year of Publication2020
AuthorsBeier UH, Hartung EA, Concors S, Hernandez PT, Wang Z, Perry C, Baur JA, Denburg MR, Hancock WW, Gade TP, Levine MH
JournalMetabolomics
Volume16
Issue5
Pagination65
Date Published2020 May 04
ISSN1573-3890
Abstract

To examine metabolic differences between renal allograft acute cellular rejection (ACR) and ischemic-reperfusion injury (IRI), we transplanted MHC-mismatched kidneys and induced 28 min warm-IRI, and collected the ACR and IRI kidneys as well as their respective native and collateral control kidneys. We extracted metabolites from the kidney tissues and found the lysine catabolite saccharopine 12.5-fold enriched in IRI kidneys, as well as the immunometabolites itaconate and kynurenine in ACR kidneys. Saccharopine accumulation is known to be toxic to mitochondria and may contribute to IRI pathophysiology, while itaconate and kynurenine may be reflective of counterregulatory responses to immune activation in ACR.

DOI10.1007/s11306-020-01682-2
Alternate JournalMetabolomics
PubMed ID32367163
Grant ListDK106243 / NH / NIH HHS / United States
OD021391 / NH / NIH HHS / United States
K23 DK109203 / DK / NIDDK NIH HHS / United States
DP5 OD021391 / OD / NIH HHS / United States
DK109203 / NH / NIH HHS / United States
AG043483 / NH / NIH HHS / United States
R01 AG043483 / AG / NIA NIH HHS / United States
R01 DK106243 / DK / NIDDK NIH HHS / United States
UL1 TR001878 / TR / NCATS NIH HHS / United States