The deubiquitinase OTUD1 stabilizes NRF2 to alleviate hepatic ischemia/reperfusion injury.
Redox Biol
; 75: 103287, 2024 Sep.
Article
en En
| MEDLINE
| ID: mdl-39079388
ABSTRACT
Hepatic ischemia/reperfusion (I/R) injury is an important cause of liver function impairment following liver surgery. The ubiquitin-proteasome system (UPS) plays a crucial role in protein quality control and has substantial impact on the hepatic I/R process. Although OTU deubiquitinase 1 (OTUD1) is involved in diverse biological processes, its specific functional implications in hepatic I/R are not yet fully understood. This study demonstrates that OTUD1 alleviates oxidative stress, apoptosis, and inflammation induced by hepatic I/R injury. Mechanistically, OTUD1 deubiquitinates and activates nuclear factor erythroid 2-related factor 2 (NRF2) through its catalytic site cysteine 320 residue and ETGE motif, thereby attenuating hepatic I/R injury. Additionally, administration of a short peptide containing the ETGE motif significantly mitigates hepatic I/R injury in mice. Overall, our study elucidates the mechanism and role of OTUD1 in ameliorating hepatic I/R injury, providing a theoretical basis for potential treatment using ETGE-peptide.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Daño por Reperfusión
/
Estrés Oxidativo
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Factor 2 Relacionado con NF-E2
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Hígado
Límite:
Animals
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Humans
/
Male
Idioma:
En
Revista:
Redox Biol
Año:
2024
Tipo del documento:
Article