PXD029232-1

PXD029232 is an original dataset announced via ProteomeXchange.

Title	L-Lysine treated rats' kidney shotgun proteome
Description	Hypertension and kidney disease, two related, common, and severe disease entities have been repeatedly associated with genomic variants and metabolic alterations of lysine metabolism. Here, we developed a stable isotope labeling strategy compatible with untargeted metabolomics acquisition to investigate the physiology and molecular spectrum of lysine’s metabolic fate in vivo. Mice received 13C6 labeled lysine through the diet over two months to track more than 100 lysine metabolites across various organs and body fluids. Globally, lysine reacts rapidly with molecules of the central carbon metabolism, as opposed to slow or incorporation into proteins and metabolization into acylcarnitines. Lysine metabolism is accelerated in the rat model of the Dahl salt-sensitive hypertension and kidney damage, chiefly through N-alpha-mediated degradation. Here, lysine administration completely diminished the development of salt-sensitive hypertension and kidney injury. Administration of lysine leads to diuresis, even further acceleration of 13C6 lysine conjugate formation, and inhibition of albumin uptake, thereby protecting from nephron injury and metabolic stress. Lysine conjugates with malonyl-CoA to form a novel metabolite N-malonyl-lysine, to deplete malonyl-CoA from fatty acid synthesis. This process occurs at the expense of protein malonylation. In hypertensive rats with kidney damage, lysine molecules were excreted as fructoselysine, saccharopine and Nε-acetyllysine, via the urine, leading to an overall depletion of central carbon metabolites from the organism and kidney. Consistent with findings in the salt-sensitive rat, lysine challenge of patients with mild kidney damage inhibited tubular albumin uptake, increased lysine conjugate formation in the urine, and reduced TCA cycle metabolites, in contrast to kidney-healthy volunteers. In conclusion, comprehensive lysine isotope tracing mapped an accelerated lysine metabolism in hypertension, and further, lysine administration induced kidney protection in kidney disease.
HostingRepository	PRIDE
AnnounceDate	2022-06-01
AnnouncementXML	Submission_2022-06-01_13:15:34.061.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD029232
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Fatih Demir
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2021-10-20 03:05:34	ID requested
⏵ 1	2022-06-01 13:15:34	announced

Dataset with its publication pending

submitter keyword: Rat, Kidney, L-Lysine, Hypertension

Markus Matthias Rinschen
contact affiliation	Aarhus University Department of Biomedicine Høegh-Guldbergsgade 10 DK-8000 Aarhus C
contact email	rinschen@biomed.au.dk
lab head
Fatih Demir
contact affiliation	Aarhus University Department of Biomedicine Markus Rinschen Lab
contact email	fatih.demir@biomed.au.dk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD029232
     1. Label: PRIDE project
     2. Name: L-Lysine treated rats' kidney shotgun proteome