HSP70, Peroxiredoxin-3 and-6 are upregulated during renal warm ischaemia in a donation after circulatory death model

Mohammad A. Hossain*, Ayesha I. De Souza, Atul Bagul, Iain A. M. MacPhee, Nicos Kessaris, Mohamed A. Morsy

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    7 Citations (Scopus)

    Abstract

    Background: The use of donation after circulatory death (DCD) kidneys for transplantation is increasing. Subsequent delayed graft function is related to ischaemia/reperfusion injury (I/R), warm ischaemia (WI) being one of the main contributing factors. This proteomics study aimed to identify candidate biomarkers of WI.

    Methods: Termination biopsies were obtained over 180 min in 6 pigs. Proteins were subjected to differential in-gel electrophoresis (DIGE) and identified using LC MS/MS.

    Results: Thirty nine protein spots showed significant changes in expression (ANOVA, p <0.05). Peroxiredoxin-3 and -6 (PRX3 and PRX6) were expressed with a fold change (FD) of +1.8 (p = 0.03 and 0.02 respectively). A significant upregulation of Alpha-2-HS-glycoprotein (A2HSG, FD + 1.9, p = 0.047) and heat-shock protein 70-1b (HSP70-1b, FD + 2.1 p = 0.002) was recorded.

    Conclusions: The expression of PRX3, PRX6 and HSP70-1b during the first 30 min of WI may be critical in measuring cellular responses. This is the first large animal model to describe the novel candidate biomarker, structural protein A2HSG. A2HSG upregulation during WI alone in this study is encouraging and further assessment in a DCD auto-transplant model is warranted.

    Biological significance

    Warm ischaemia (WI) during donation after circulatory death (DCD) organ retrieval is associated with higher rates of post transplant organ dysfunction. The cellular and molecular mechanism of this paradigm is poorly reported. The work carried out in this large animal study has been performed to enable better understanding of protein expression during DCD WI at the time of retrieval. We have identified differential increased expression of PRX3, PRX6 and HSP70 during the first 30 min of WI. Observation of this behaviour has not been reported before. Application of these results in a reperfusion model or autograft animal study would further help study of the named proteins as clinical biomarkers of WI. Alpha 2-HS Glycoprotein (A2HSG) species were also differentially expressed during the WI period. This remains a novel finding. Assessment of A2HSG is also recommended for further study in a reperfusion context. Previous reports of A2HSG have suggested an association in chronic kidney disease and diabetes, but no association with WI has previously been noted in either small or large animals. (C) 2014 Elsevier B.V. All rights reserved.

    Original languageEnglish
    Pages (from-to)133-145
    Number of pages13
    JournalJournal Of Proteomics
    Volume108
    DOIs
    Publication statusPublished - 28 Aug 2014

    Keywords

    • Renal transplantation
    • Warm ischaemia
    • Experimental model
    • Donation after circulatory death
    • HEAT-SHOCK PROTEINS
    • ACUTE KIDNEY INJURY
    • GELATINASE-ASSOCIATED LIPOCALIN
    • REPERFUSION INJURY
    • BEATING DONOR
    • MOLECULAR CHAPERONES
    • URINARY BIOMARKER
    • OXIDATIVE STRESS
    • MESSENGER-RNA
    • CARDIAC DEATH

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