Programmed necrosis in acute kidney injury.
Nephrol Dial Transplant
; 27(9): 3412-9, 2012 Sep.
Article
en En
| MEDLINE
| ID: mdl-22942173
ABSTRACT
Programmed cell death (PCD) had been widely used synonymously to caspase-mediated apoptosis until caspase-independent cell death was described. Identification of necrosis as a regulated process in ischaemic conditions has recently changed our understanding of PCD. At least three pathways of programmed necrosis (PN) have been identified. First, receptor-interacting protein kinase 3 (RIP3)-dependent necroptosis causes organ failure following stroke, myocardial infarction and renal ischaemia/reperfusion injury. Necroptosis can be mediated either by a large intracellular caspase-8-containing signalling complex called the ripoptosome or by the RIP1-/RIP3-containing necroptosome and is controlled by a caspase-8/FLICE inhibitory protein(long) heterodimer at least in the latter case. Second, mitochondrial permeability transition mediates apoptotic or necrotic stimuli and depends on the mitochondrial protein cyclophilin D. The third PN pathway involves the poly(ADP-ribose) polymerase-calpain axis that contributes to acute kidney injury (AKI). Preclinical interference with the PN pathways therefore raises expectations for the future treatment of ischaemic conditions. In this brief review, we aim to summarize the clinically relevant PCD pathways and to transfer the basic science data to settings of AKI. We conclude that pathologists were quite right to refer to ischaemic kidney injury as 'acute tubular necrosis'.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Lesión Renal Aguda
/
Necrosis
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Nephrol Dial Transplant
Asunto de la revista:
NEFROLOGIA
/
TRANSPLANTE
Año:
2012
Tipo del documento:
Article