Open AccessNAD + ameliorates endotoxin‐induced acute kidney injury in a sirtuin1–dependent manner via GSK‐3β/Nrf2 signalling pathway
Author(s) -
He Simeng,
Gao Qiaoying,
Wu Xiaoyang,
Shi Jia,
Zhang Yuan,
Yang Jing,
Li Xiangyun,
Du Shihan,
Zhang Yanfang,
Yu Jianbo
Publication year - 2022
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.17222
Subject(s) - nad+ kinase , sirtuin 1 , oxidative stress , acute kidney injury , sirtuin , pharmacology , kidney , medicine , apoptosis , chemistry , gsk 3 , downregulation and upregulation , cancer research , biochemistry , signal transduction , enzyme , gene
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‐3β (GSK‐3β) that was concomitant with mitigated Nrf2 nuclear accumulation, thereby exacerbates AKI. These findings suggest that NAD + /SIRT1/GSK‐3β/Nrf2 axis is an important mechanism that can protect against AKI which might be a potential therapeutic target for the treatment of AKI.