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

الملخص EN

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_RAT, RSSA_RAT, F16P1_RAT, STML2_RAT, BPNT1_RAT, LGMN_RAT, ATPA_RAT, and VDAC1_RAT) were downregulated and six proteins (MTUS1_RAT, F16P1_RAT, ACTG_RAT, ACTB_RAT, 2ABA_RAT, and RAB1A_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.