Abstract
Administration of oxygen is one of the most common interventions in medicine. Previous research showed that differential regulated proteins could be linked to hyperoxia-associated signaling cascades in different tissues. However, it still remains unclear which signaling pathways are activated by hyperoxia. The present study analyses hyperoxia-induced protein alterations in lung, brain, and kidney tissue using a proteomic and bioinformatic approach. Pooled data of 36 Wistar rats exposed to hyperoxia were used. To identify possible hyperoxia biomarkers, and to evaluate the relationship between protein alterations in hyperoxia affected organs and blood, proteomics data from brain, lung, and kidney were analyzed. Functional network analyses (IPA®, PathwaysStudio®, and GENEmania®) in combination with hierarchical cluster analysis (Perseus®) was used to identify relevant pathways and key proteins. Data of 54 2D-gels with more than 2500 significantly regulated spots per gel were collected. Thirty-eight differentially expressed proteins were identified and consecutively analyzed by bioinformatic methods. Most differences between hyperoxia and normoxia (21 proteins up-regulated, 17 proteins down-regulated) were found immediately after hyperoxia (15 protein spots), followed by day 3 (13 spots), and day 7 (10 spots). A highly significant association with inflammation and the inflammatory response was found. Cell proliferation, oxidative stress, apoptosis and cell death as well as cellular functions were revealed to be affected. Three hours of hyperoxia resulted in significant alterations of protein expression in different organs (brain, lung, kidney) up to seven days after exposure. Further studies are required to interpret the relevance of protein alterations in signaling cascades during/after hyperoxia.
Highlights
The application of oxygen is one of the most common interventions in medicine, both in pre-hospital and in-hospital settings
The following methodology was used: after weighing, 18 animals were randomly assigned to three normobaric hyperoxia groups (NH) and the remaining 18 rats were allocated to three normobaric normoxia groups (NN)
The results of the present study satisfactorily show a relevant change in protein expression after 3 h normobaric hyperoxia that remains detectable for up to 7 days
Summary
The application of oxygen is one of the most common interventions in medicine, both in pre-hospital and in-hospital settings. While the cellular oxygen supply represents one mainstay of survival, hyperoxia has a deleterious potential [1,2,3]. The risks of hyperoxia in critically ill and emergency patients have been intensively discussed [1,2,3,4,5]. Hyperoxia gained significant interest during the post-resuscitation period. Increased levels of oxygen partial pressure lead to worse outcomes [2,3,4,5]. Arterial hyperoxia may be associated with an increased mortality in critically ill patients [1]
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