Protection of the transplant kidney during cold perfusion with doxycycline: proteomic analysis in a rat model.

Proteome Sci

2Department of Anatomy, Physiology and Pharmacology, University of Saskatchewan, Saskatoon, 107 Wiggins Road, Saskatoon, Saskatchewan S7N 5E5 Canada.

Published: April 2020

AI Article Synopsis

  • - The study investigates how doxycycline (Doxy) protects kidneys from preservation injury by looking for molecular targets involved in the injury mechanism.
  • - Rat kidneys were analyzed after being cold perfused with or without Doxy, checking for injury markers and using advanced protein analysis techniques.
  • - The results identified key metabolic enzymes that are influenced by Doxy during kidney preservation, suggesting its role in mitigating injury through specific molecular pathways.

Article Abstract

Background: It has been previously shown that doxycycline (Doxy) protects the kidney from preservation injury by inhibition of matrix metalloproteinase. However, the precise molecular mechanism involved in this protection from injury is not known. We used a pharmaco-proteomics approach to identify potential molecular targets associated with kidney preservation injury.

Methods: Rat kidneys were cold perfused with or without doxycycline (Doxy) for 22 h. Kidneys perfusates were analyzed for the presence of injury markers such as lactate dehydrogenase (LDH), and neutrophil-gelatinase associated lipocalin (NGAL). Proteins extracted from kidney tissue were analyzed by 2-dimensional gel electrophoresis. Proteins of interest were identified by mass spectrometry.

Results: Triosephosphate isomerase, PGM, dihydropteridine reductase-2, pyridine nucleotide-disulfide oxidoreductase, phosphotriesterase-related protein, and aminoacylase-1A were not affected by cold perfusion. Perfusion with Doxy increased their levels. N(G),N(G)-dimethylarginine dimethylaminohydrolase and phosphoglycerate kinase 1 were decreased after cold perfusion. Perfusion with Doxy led to an increase in their levels.

Conclusions: This study revealed specific metabolic enzymes involved in preservation injury and in the mechanism whereby Doxy protects the kidney against injury during cold perfusion.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7171734PMC
http://dx.doi.org/10.1186/s12953-020-00159-3DOI Listing

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