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Proteo-metabolomics reveals compensation between ischemic and non-injured contralateral kidneys after reperfusion.

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.

SUBMITTER: Huang H

PROVIDER: S-EPMC5986744 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Proteo-metabolomics reveals compensation between ischemic and non-injured contralateral kidneys after reperfusion.

Huang Honglei H van Dullemen Leon F A LFA Akhtar Mohammed Z MZ Faro Maria-Letizia Lo ML Yu Zhanru Z Valli Alessandro A Dona Anthony A Thézénas Marie-Laëtitia ML Charles Philip D PD Fischer Roman R Kaisar Maria M Leuvenink Henri G D HGD Ploeg Rutger J RJ Kessler Benedikt M BM

Scientific reports 20180604 1

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 mi ...[more]

PMID: 29867102

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Project description:IntroductionThe effects of exercise on the heart and its resistance to disease are well-documented. Recent studies have identified that exercise-induced resistance to arrhythmia is due to the preservation of mitochondrial membrane potential.ObjectivesTo identify novel metabolic changes that occur parallel to these mitochondrial alterations, we performed non-targeted metabolomics analysis on hearts from sedentary and exercise-trained rats challenged with isolated heart ischemia-reperfusion injury (I/R).MethodsEight-week old Sprague-Dawley rats were treadmill trained 5 days/week for 6 weeks (exercise duration and intensity progressively increased to 1 h at 30 m/min up a 10.5% incline, 75-80% VO2max). The recovery of pre-ischemic function for sedentary rat hearts was 28.8 ± 5.4% (N = 12) compared to exercise trained hearts, which recovered 51.9% ± 5.7 (N = 14) (p < 0.001).ResultsNon-targeted GC-MS metabolomics analysis of (1) sedentary rat hearts; (2) exercise-trained rat hearts; (3) sedentary rat hearts challenged with global ischemia-reperfusion (I/R) injury; and (4) exercise-trained rat hearts challenged with global I/R (10/group) revealed 15 statistically significant metabolites between groups by ANOVA using Metaboanalyst (p < 0.001). Enrichment analysis of these metabolites for pathway-associated metabolic sets indicated a > 10-fold enrichment for ammonia recycling and protein biosynthesis. Subsequent comparison of the sedentary hearts post-I/R and exercise-trained hearts post-I/R further identified significant differences in three metabolites (oleic acid, pantothenic acid, and campesterol) related to pantothenate and CoA biosynthesis (p ≤ 1.24E-05, FDR ≤ 5.07E-4).ConclusionsThese studies shed light on novel mechanisms in which exercise-induced cardioprotection occurs in I/R that complement both the mitochondrial stabilization and antioxidant mechanisms recently described. These findings also link protein synthesis and protein degradation (protein quality control mechanisms) with exercise-linked cardioprotection and mitochondrial susceptibility for the first time in cardiac I/R.

Dataset Information

Proteo-metabolomics reveals compensation between ischemic and non-injured contralateral kidneys after reperfusion.

Publications

Proteo-metabolomics reveals compensation between ischemic and non-injured contralateral kidneys after reperfusion.

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