Intestinal ischemia reperfusion injury (iIRI) is a severe clinical condition presenting high morbidity and mortality worldwide. Some of the systemic consequences of iIRI can be prevented by applying ischemic preconditioning (iIPC), a series of short ischemia/reperfusion events preceding the major ischemia. Although neutrophils are key players in the physiopathology of ischemic injuries, neither the dysregulation presented by these cells in iIRI nor the protective effect of iIPC have their regulation mechanisms fully understood. Protein phosphorylation, as well as the regulation of the respective phosphatases and kinases are responsible for regulating a large number of cellular functions in the inflammatory response. Therefore, in the present study we analyzed the phosphoproteome of neutrophils from rats submitted to mesenteric ischemia and reperfusion, either submitted or not to IPC, compared to quiescent controls and sham laparotomy. Proteomic analysis was performed by multi-step enrichment of phosphopeptides, isobaric labeling and LC-MS/MS analysis. Bioinformatics was used to determine phosphosite and phosphopeptide abundance and clustering, as well as kinases and phosphatases sites and domains. We found that most of the phosphorylation-regulated proteins are involved in apoptosis and migration, and most of the regulatory kinases belong to CAMK and CMGC families. Some relevant regulatory proteins discussed are Vamp8, PKC delta, NDR1/Stk38 and Inpp5c/Shipp
[doi:10.25345/C5CD5Z]
[dataset license: CC0 1.0 Universal (CC0 1.0)]
Keywords: inflammatory response ; neutrophil ; phosphatases ; kinases
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Principal Investigators: (in alphabetical order) |
Wagner Fontes, UnB, Brazil |
| Submitting User: | LBQP_Wagner_phosphoIPC |
Tahir M, Arshid S, Fontes B, S Castro M, Sidoli S, Schwämmle V, Luz IS, Roepstorff P, Fontes W.
Phosphoproteomic Analysis of Rat Neutrophils Shows the Effect of Intestinal Ischemia/Reperfusion and Preconditioning on Kinases and Phosphatases.
Int J Mol Sci. Epub 2020 Aug 13.
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