Hyperoxia-Induced Protein Alterations in Renal Rat Tissue: A Quantitative Proteomic Approach to Identify Hyperoxia-Induced Effects in Cellular Signaling Pathways.

Introduction: In renal tissue as well as in other organs, supranormal oxygen pressure may lead to deleterious consequences on a cellular level. Additionally, hyperoxia-induced effect in cells and related free radicals may potentially contribute to renal failure. The aim of this study was to analyze time-dependent alterations of rat kidney protein expression after short-term normobaric hyperoxia using proteomics and bioinformatic approaches.
Material and Methods: N = 36 Wistar rats were randomized into six different groups: three groups with normobaric hyperoxia (exposure to 100% oxygen for 3 h) and three groups with normobaric normoxia (NN; room air). After hyperoxia exposure, kidneys were removed immediately, after 3 days and after 7 days. Kidney lysates were analyzed by two-dimensional gel electrophoresis followed by peptide mass fingerprinting using tandem mass spectrometry. Statistical analysis was performed with DeCyder 2D software (p < 0.01). Biological functions of differential regulated proteins were studied using functional network analysis (Ingenuity Pathways Analysis and PathwayStudio).
Results: Expression of 14 proteins was significantly altered (p < 0.01): eight proteins (MEP1A&#95;RAT, RSSA&#95;RAT, F16P1&#95;RAT, STML2&#95;RAT, BPNT1&#95;RAT, LGMN&#95;RAT, ATPA&#95;RAT, and VDAC1&#95;RAT) were downregulated and six proteins (MTUS1&#95;RAT, F16P1&#95;RAT, ACTG&#95;RAT, ACTB&#95;RAT, 2ABA&#95;RAT, and RAB1A&#95;RAT) were upregulated. Bioinformatic analyses revealed an association of regulated proteins with inflammation.
Conclusions: Significant alterations in renal protein expression could be demonstrated for up to 7 days even after short-term hyperoxia. The identified proteins indicate an association with inflammation signaling cascades. MEP1A and VDAC1 could be promising candidates to identify hyperoxic injury in kidney cells.