PMID- 30487750
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 1664-042X (Print)
IS  - 1664-042X (Electronic)
IS  - 1664-042X (Linking)
VI  - 9
DP  - 2018
TI  - SIRT3 Protects Against Acute Kidney Injury via AMPK/mTOR-Regulated Autophagy.
PG  - 1526
LID - 10.3389/fphys.2018.01526 [doi]
LID - 1526
AB  - Acute kidney injury (AKI), which involves the loss of kidney function caused by 
      damage to renal tubular cells, is an important public health concern. We 
      previously showed that sirtuin (SIRT)3 protects the kidneys against mitochondrial 
      damage by inhibiting the nucleotide-binding domain (NOD)-like receptor protein 3 
      (NLRP3) inflammasome, attenuating oxidative stress, and downregulating 
      proinflammatory cytokines. In this article, we investigated the role of 
      autophagy, mediated by a mammalian target of rapamycin (mTOR) and AMP-activated 
      protein kinase (AMPK), in the protective effect of SIRT3, against sepsis-induced 
      AKI, in a mouse model of cecal ligation and puncture (CLP). The AKI in CLP mice 
      was associated with the upregulation of autophagy markers; this effect was 
      abolished in SIRT3(-) mice in parallel with the downregulation of phospho 
      (p)-AMPK and the upregulation of p-mTOR. Pretreatment with the autophagy 
      inhibitor 3-methyladenine (3-MA) or AMPK inhibitor compound isotonic saline (C), 
      exacerbated AKI. SIRT3 overexpression promoted autophagy, upregulated p-AMPK and 
      downregulated p-mTOR in CLP mice, attenuating sepsis-induced AKI, tubular cell 
      apoptosis, and inflammatory cytokine accumulation in the kidneys. The blockage of 
      autophagy induction largely abolished the protective effect of SIRT3 in 
      sepsis-induced AKI. These findings indicate that SIRT3 protects against 
      CLP-induced AKI by inducing autophagy through regulation of the AMPK/mTOR 
      pathway.
FAU - Zhao, Wenyu
AU  - Zhao W
AD  - Department of Organ Transplantation, Changhai Hospital, Second Military Medical 
      University, Shanghai, China.
FAU - Zhang, Lei
AU  - Zhang L
AD  - Department of Organ Transplantation, Changhai Hospital, Second Military Medical 
      University, Shanghai, China.
FAU - Chen, Rui
AU  - Chen R
AD  - Department of Organ Transplantation, Changhai Hospital, Second Military Medical 
      University, Shanghai, China.
FAU - Lu, Hanlan
AU  - Lu H
AD  - Department of Organ Transplantation, Changhai Hospital, Second Military Medical 
      University, Shanghai, China.
FAU - Sui, Mingxing
AU  - Sui M
AD  - Department of Organ Transplantation, Changhai Hospital, Second Military Medical 
      University, Shanghai, China.
FAU - Zhu, Youhua
AU  - Zhu Y
AD  - Department of Organ Transplantation, Changhai Hospital, Second Military Medical 
      University, Shanghai, China.
FAU - Zeng, Li
AU  - Zeng L
AD  - Department of Organ Transplantation, Changhai Hospital, Second Military Medical 
      University, Shanghai, China.
LA  - eng
PT  - Journal Article
DEP - 20181114
PL  - Switzerland
TA  - Front Physiol
JT  - Frontiers in physiology
JID - 101549006
PMC - PMC6246697
OTO - NOTNLM
OT  - AMPK/mTOR pathway
OT  - acute kidney injury
OT  - autophagy
OT  - cecal ligation and puncture
OT  - sirtuin 3
EDAT- 2018/11/30 06:00
MHDA- 2018/11/30 06:01
PMCR- 2018/11/14
CRDT- 2018/11/30 06:00
PHST- 2018/03/18 00:00 [received]
PHST- 2018/10/11 00:00 [accepted]
PHST- 2018/11/30 06:00 [entrez]
PHST- 2018/11/30 06:00 [pubmed]
PHST- 2018/11/30 06:01 [medline]
PHST- 2018/11/14 00:00 [pmc-release]
AID - 10.3389/fphys.2018.01526 [doi]
PST - epublish
SO  - Front Physiol. 2018 Nov 14;9:1526. doi: 10.3389/fphys.2018.01526. eCollection 
      2018.