Protective role of DJ-1 in endotoxin-induced acute kidney injury.
Am J Physiol Renal Physiol
; 319(4): F654-F663, 2020 10 01.
Article
in En
| MEDLINE
| ID: mdl-32715759
ABSTRACT
Acute kidney injury (AKI) is a frequent complication of sepsis and an important cause of morbidity and mortality worldwide. A cornerstone of sepsis-associated AKI is dysregulated inflammation, leading to increased tissue oxidative stress and free radical formation, which leads to multiple forms of cell death. DJ-1 is a peroxiredoxin protein with multiple functions, including its ability to control cellular oxidative stress. Although DJ-1 is expressed prominently by renal tubules, its role in AKI has not been investigated. In the present study, we examined the effect of DJ-1 deficiency in a murine model of endotoxin-induced AKI. Endotoxemia induced greater kidney injury in DJ-1-deficient mice. Furthermore, DJ-1 deficiency increased renal oxidative stress associated with increased renal tubular apoptosis and with expression of death domain-associated protein (DAXX). Similar to the in vivo model, in vitro experiments using a medullary collecting duct cell line (mIMCD3) and cytotoxic serum showed that serum obtained from wild-type mice resulted in increased expression of s100A8/s100A9, DAXX, and apoptosis in DJ-1-deficient mIMCD3 cells. Our findings demonstrate a novel renal protective role for renal tubular DJ-1 during endotoxemia through control of oxidative stress, renal inflammation, and DAXX-dependent apoptosis.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Lipopolysaccharides
/
Endotoxemia
/
Acute Kidney Injury
/
Protein Deglycase DJ-1
/
Kidney Tubules
/
Nephritis
Type of study:
Etiology_studies
/
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Am J Physiol Renal Physiol
Journal subject:
FISIOLOGIA
/
NEFROLOGIA
Year:
2020
Document type:
Article