Using an Integrated-Omics Approach to Identify Key Cellular Processes That Are Disturbed in the Kidney After Brain Death

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dc.contributor.authorAkhtar, M. Z.
dc.contributor.authorHuang, H.
dc.contributor.authorKaisar, M.
dc.contributor.authorLo Faro, M. L.
dc.contributor.authorRebolledo Acevedo, Rolando Arturo
dc.contributor.authorMorten, K.
dc.contributor.authorHeather, L. C.
dc.contributor.authorDona, A.
dc.contributor.authorLeuvenink, H. G.
dc.contributor.authorFuggle, S. V.
dc.contributor.authorKessler, B. M.
dc.contributor.authorPugh, C. W.
dc.contributor.authorPloeg, R. J.
dc.date.accessioned2023-01-13T19:14:43Z
dc.date.available2023-01-13T19:14:43Z
dc.date.issued2016
dc.description.abstractIn an era where we are becoming more reliant on vulnerable kidneys for transplantation from older donors, there is an urgent need to understand how brain death leads to kidney dysfunction and, hence, how this can be prevented. Using a rodent model of hemorrhagic stroke and next-generation proteomic and metabolomic technologies, we aimed to delineate which key cellular processes are perturbed in the kidney after brain death. Pathway analysis of the proteomic signature of kidneys from brain-dead donors revealed large-scale changes in mitochondrial proteins that were associated with altered mitochondrial activity and morphological evidence of mitochondrial injury. We identified an increase in a number of glycolytic proteins and lactate production, suggesting a shift toward anaerobic metabolism. Higher amounts of succinate were found in the brain death group, in conjunction with increased markers of oxidative stress. We characterized the responsiveness of hypoxia inducible factors and found this correlated with post-brain death mean arterial pressures. Brain death leads to metabolic disturbances in the kidney and alterations in mitochondrial function and reactive oxygen species generation. This metabolic disturbance and alteration in mitochondrial function may lead to further cellular injury. Conditioning the brain-dead organ donor by altering metabolism could be a novel approach to ameliorate this brain death-induced kidney injury.
dc.fuente.origenSIPA
dc.identifier.doi10.1111/ajt.13626
dc.identifier.urihttps://doi.org/10.1111/ajt.13626
dc.identifier.urihttps://onlinelibrary.wiley.com/doi/10.1111/ajt.13626
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/66305
dc.information.autorucEscuela de medicina ; Rebolledo Acevedo, Rolando Arturo ; 0000-0003-3501-4042 ; 127520
dc.issue.numero5
dc.language.isoen
dc.nota.accesoContenido completo
dc.pagina.final1440
dc.pagina.inicio1421
dc.revistaAmerican Journal of Transplantationes_ES
dc.rightsacceso abierto
dc.titleUsing an Integrated-Omics Approach to Identify Key Cellular Processes That Are Disturbed in the Kidney After Brain Deathes_ES
dc.typeartículo
dc.volumen5
sipa.codpersvinculados127520
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