Abstract
Ischaemia and reperfusion injury (IRI) is the leading cause of acute kidney injury (AKI), which contributes to high morbidity and mortality rates in a wide range of injuries as well as the development of chronic kidney disease. The cellular and molecular responses of the kidney to IRI are complex and not fully understood. Here, we used an integrated proteomic and metabolomic approach to investigate the effects of IRI on protein abundance and metabolite levels. Rat kidneys were subjected to 45 min of warm ischaemia followed by 4 h and 24 h reperfusion, with contralateral and separate healthy kidneys serving as controls. Kidney tissue proteomics after IRI revealed elevated proteins belonging to the acute phase response, coagulation and complement pathways, and fatty acid (FA) signalling. Metabolic changes were already evident after 4 h reperfusion and showed increased level of glycolysis, lipids and FAs, whilst mitochondrial function and ATP production was impaired after 24 h. This deficit was partially compensated for by the contralateral kidney. Such a metabolic balance counteracts for the developing energy deficit due to reduced mitochondrial function in the injured kidney.
Highlights
Metabolic changes including lactate, succinate, choline, taurine and fatty acids have been observed after renal ischemic insults[5,17,18]
This trait was not observed in 4 h-Ischaemia and reperfusion injury (IRI) or the control kidneys (4 h-C, 24 h-C, healthy control (HC)) (Figure S1)
This was consistent with the level of injury observed in the histological sections of the same area stained with Periodic Acid Schiff (PAS)
Summary
Metabolic changes including lactate, succinate, choline, taurine and fatty acids have been observed after renal ischemic insults[5,17,18]. A more comprehensive study that integrates proteomic and metabolomic alterations at the initial stages of reperfusion after an ischemic insult has not yet been carried out in a more systematic fashion. We used a non-lethal unilateral long IRI model in the rat[19] and carried out an unbiased integrative proteo-metabolomic study in combination with mitochondrial function analysis of kidneys exposed to IRI to investigate its effects at the molecular level
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