PXD029599

PXD029599 is an original dataset announced via ProteomeXchange.

Title	Doxycycline alters porcine renal proteome and degradome during hypothermic machine perfusion
Description	Ischemia/reperfusion injury (IRI) is a hallmark of tissue injury in donation after circulatory death (DCD) kidneys. The implementation of hypothermic machine perfusion (HMP) provides a platform for repair of DCD kidneys. Doxycycline administration has shown protective effects during IRI. Here, we explore the impact of doxycycline on proteolytic degradation mechanisms and the urinary proteome of perfused kidney grafts. Porcine kidneys underwent 30 min of warm ischemia, 24 h of oxygenated HMP (control/doxycycline) and 240 min of ex-vivo reperfusion. A high-efficiency undecanal-based N-termini enrichment workflow (HUNTER) was performed to identify the tissue degradome. In addition, a proteomic analysis was applied on urine samples collected during reperfusion using label-free quantitation (LFQ) mass spectrometry. Hierarchical clustering showed distinctive clustering profiles between urine samples collected at T15 min (metabolism) and T240 min (complement and coagulation). At T10, significantly more degraded proteins were observed in perfusates of the control group. At T240, significantly more degraded proteins were observed in the doxycycline group, indicating that doxycycline alters protein degradation during HMP. In conclusion, doxycycline administration during HMP led to significant proteomic differences including protective effects by attenuating urinary NGAL levels. Ultimately, we unravelled multiple pathways that undergo alterations during machine perfusion that can be targeted to attenuate IRI induced injury.
HostingRepository	PRIDE
AnnounceDate	2022-08-12
AnnouncementXML	Submission_2022-08-11_23:54:47.547.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Leonie van Leeuwen
SpeciesList	scientific name: Sus scrofa domesticus (domestic pig); NCBI TaxID: 9825;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-11-05 13:07:40	ID requested
⏵ 1	2022-08-11 23:54:48	announced

van Leeuwen L, Venema LH, Heilig R, Leuvenink HGD, Kessler BM, Doxycycline Alters the Porcine Renal Proteome and Degradome during Hypothermic Machine Perfusion. Curr Issues Mol Biol, 44(2):559-577(2022) [pubmed]

submitter keyword: Renal transplantation

ischemia/reperfusion injury

machine perfusion

proteomics

Prof. Dr. B.M. Kessler
contact affiliation	Target Discovery Institute, Centre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7FZ, UK
contact email	benedikt.kessler@ndm.ox.ac.uk
lab head
Leonie van Leeuwen
contact affiliation	University Medical Center Groningen
contact email	l.l.van.leeuwen@umcg.nl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD029599
     1. Label: PRIDE project
     2. Name: Doxycycline alters porcine renal proteome and degradome during hypothermic machine perfusion