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PXD029599

PXD029599 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleDoxycycline alters porcine renal proteome and degradome during hypothermic machine perfusion
DescriptionIschemia/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.
HostingRepositoryPRIDE
AnnounceDate2022-08-12
AnnouncementXMLSubmission_2022-08-11_23:54:47.547.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterLeonie van Leeuwen
SpeciesList scientific name: Sus scrofa domesticus (domestic pig); NCBI TaxID: 9825;
ModificationListNo PTMs are included in the dataset
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-11-05 13:07:40ID requested
12022-08-11 23:54:48announced
Publication List
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]
Keyword List
submitter keyword: Renal transplantation
ischemia/reperfusion injury
machine perfusion
proteomics
Contact List
Prof. Dr. B.M. Kessler
contact affiliationTarget Discovery Institute, Centre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7FZ, UK
contact emailbenedikt.kessler@ndm.ox.ac.uk
lab head
Leonie van Leeuwen
contact affiliationUniversity Medical Center Groningen
contact emaill.l.van.leeuwen@umcg.nl
dataset submitter
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