Activity-based protein profiling of intraoperative serine hydrolase activities during cardiac surgery

dc.contributor.authorNavarette, Mario
dc.contributor.authorHo, Julie
dc.contributor.authorDwivedi, Ravi
dc.contributor.authorChoi, Nora
dc.contributor.authorEzzati, Peyman
dc.contributor.authorKrokhin, Oleg
dc.contributor.authorSpicer, Vic
dc.contributor.authorArora, Rakesh
dc.contributor.authorRigatto, Claudio
dc.contributor.authorWilkins, John
dc.description.abstractThe processes involved in the initiation of acute kidney injury (AKI) following cardiopulmonary bypass (CPB) are thought to occur during the intraoperative period. Such a rapid development might indicate that some of the inductive events are not dependent on de novo protein synthesis, raising the possibility that changes in activities of pre-existing enzymes could contribute to the development of AKI. Activity-based protein profiling (ABPP) was used to compare the serine hydrolase enzyme activities present in the urines of CPB patients who subsequently developed AKI versus those who did not (non-AKI) during the intra- and immediate postoperative periods. Sequential urines collected from a nested case-control cohort of AKI and non-AKI patients were reacted with a serine hydrolase activity probe, fluorophosphonate-TAMRA, and separated by SDS-PAGE. The patterns and levels of probe-labeled proteins in the two groups were initially comparable. However, within 1 h of CPB there were significant pattern changes in the AKI group. Affinity purification and mass spectrometry-based analysis of probe-labeled enzymes in AKI urines at 1 h CPB and arrival to the intensive care unit (ICU) identified 28 enzymes. Quantitative analysis of the activity of one of the identified enzymes, kallikrein-1, revealed some trends suggesting differences in the levels and temporal patterns of enzyme activity between a subset of patients who developed AKI and those who did not. A comparative analysis of affinity-purified probe reacted urinary proteins from these patient groups during the intraoperative period suggested the presence of both shared and unique enzyme patterns. These results indicate that there are intraoperative changes in the levels and types of serine hydrolase activities in patients who subsequently develop AKI. However, the role of these activity differences in the development of AKI remains to be determined.en_US
dc.description.sponsorshipResearch Manitoba Establishment grant. Kidney Foundation of Canada. Canadian Institutes of Health Research (#287559). Canadian Institutes of Health Research New Investigator Salary Award (#340137).en_US
dc.identifier.citationJ Proteome Res 17(10): 3547-3556, 2018en_US
dc.publisherAmerican Chemical Society Publicationsen_US
dc.rightsopen accessen_US
dc.subjectactivity-based protein profilingen_US
dc.subjectacute kidney injuryen_US
dc.subjectserine hydrolaseen_US
dc.subjectcardiopulmonary bypassen_US
dc.titleActivity-based protein profiling of intraoperative serine hydrolase activities during cardiac surgeryen_US
dc.typeresearch articleen_US
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