NAD+ ameliorates endotoxin-induced acute kidney injury in a sirtuin1-dependent manner via GSK-3ß/Nrf2 signalling pathway.
J Cell Mol Med
; 26(7): 1979-1993, 2022 04.
Article
in English
| MEDLINE | ID: covidwho-1774827
ABSTRACT
Acute kidney injury (AKI) is a substantial worldwide public health concern with no specific and effective therapies in clinic. NAD+ is a pivotal determinant of cellular energy metabolism involved in the progression of AKI; however, its mechanism in kidney injury remains poorly understood. Sirtuin 1 (SIRT1) is an NAD+ -dependent deacetylase associated with renal protection and acute stress resistance. In this study, we have investigated the role of NAD+ in AKI and the potential mechanism(s) involved in its renoprotective effect. NAD+ was notably decreased and negatively correlated with kidney dysfunction in AKI, restoring NAD+ with NMN significantly ameliorates LPS-induced oxidative stress and apoptosis and attenuates renal damage. We also found that the protection of NAD+ is associated with SIRT1 expressions and performs in a SIRT1-dependent manner. Inhibition of SIRT1 blunted the protective effect of NAD+ and up-regulated the activity of glycogen synthase kinase-3ß (GSK-3ß) that was concomitant with mitigated Nrf2 nuclear accumulation, thereby exacerbates AKI. These findings suggest that NAD+ /SIRT1/GSK-3ß/Nrf2 axis is an important mechanism that can protect against AKI which might be a potential therapeutic target for the treatment of AKI.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
NF-E2-Related Factor 2
/
Sirtuin 1
/
Acute Kidney Injury
/
Glycogen Synthase Kinase 3 beta
/
NAD
Limits:
Humans
Language:
English
Journal:
J Cell Mol Med
Journal subject:
Molecular Biology
Year:
2022
Document Type:
Article
Affiliation country:
Jcmm.17222
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