Kynurenine 3-monooxygenase is a critical regulator of renal ischemia-reperfusion injury.
Exp Mol Med
; 51(2): 1-14, 2019 02 13.
Article
em En
| MEDLINE
| ID: mdl-30760699
ABSTRACT
Acute kidney injury (AKI) following ischemia-reperfusion injury (IRI) has a high mortality and lacks specific therapies. Here, we report that mice lacking kynurenine 3-monooxygenase (KMO) activity (Kmonull mice) are protected against AKI after renal IRI. We show that KMO is highly expressed in the kidney and exerts major metabolic control over the biologically active kynurenine metabolites 3-hydroxykynurenine, kynurenic acid, and downstream metabolites. In experimental AKI induced by kidney IRI, Kmonull mice had preserved renal function, reduced renal tubular cell injury, and fewer infiltrating neutrophils compared with wild-type (Kmowt) control mice. Together, these data confirm that flux through KMO contributes to AKI after IRI, and supports the rationale for KMO inhibition as a therapeutic strategy to protect against AKI during critical illness.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Traumatismo por Reperfusão
/
Quinurenina 3-Mono-Oxigenase
/
Nefropatias
Limite:
Animals
Idioma:
En
Revista:
Exp Mol Med
Assunto da revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Reino Unido