PMID- 30483738
OWN - NLM
STAT- MEDLINE
DCOM- 20190524
LR  - 20211018
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Print)
IS  - 1791-2997 (Linking)
VI  - 19
IP  - 2
DP  - 2019 Feb
TI  - A SIRT1 agonist reduces cognitive decline in type 2 diabetic rats through 
      antioxidative and anti‑inflammatory mechanisms.
PG  - 1040-1048
LID - 10.3892/mmr.2018.9699 [doi]
AB  - Sirtuin 1 (SIRT1) is an NAD+‑dependent protein deacetylase that is involved in 
      cell differentiation, aging, apoptosis, physiological rhythms, metabolic 
      regulation, oxidative stress and numerous other important biological processes. 
      In the present study, the ability of a sirtuin‑1 (SIRT1) agonist, SRT1720, to 
      reduce cognitive decline in type 2 diabetes mellitus (T2DM) was investigated. 
      Streptozotocin‑induced male Sprague‑Dawley rats were used to establish a T2DM 
      model and the protective effect of SRT1720 and its underlying mechanisms were 
      investigated. Body weight and fasting blood glucose (FBG) were recorded and 
      cognitive function was measured with the Morris water maze. Levels of oxidative 
      stress, inflammation, caspase‑3 activity and nuclear factor kappaB (NF‑kappaB) mRNA 
      expression were detected with a series of commercial assay kits and reverse 
      transcription‑quantitative polymerase chain reaction, respectively. Western blot 
      analysis was performed to determine the protein expression of NF‑kappaB, endothelial 
      nitric oxide synthase (eNOS), peroxisome proliferator‑activated receptor gamma 
      (PPARgamma), AMP‑activated protein kinase (AMPK), heat shock 70 kDa protein (HSP70), 
      SIRT1, nuclear factor erythroid 2‑related factor 2 (Nrf2) and heme oxygenase 1 
      (HO‑1). The results revealed that SRT1720 significantly increased body weight, 
      decreased FBG, improved cognitive function and reduced the levels of proteins 
      associated with oxidative stress and inflammation damage in T2DM rats. 
      Additionally, SRT1720 significantly decreased NF‑kappaB p65 mRNA expression and 
      increased eNOS and PPARgamma expression. SRT1720 significantly reduced caspase‑3 
      activity and HSP70 protein expression, and increased p‑AMPK, SIRT1, Nrf2 and HO‑1 
      protein expression. Collectively, the results indicate that SRT1720 may reduce 
      cognitive decline in T2DM rats through antioxidative and anti‑inflammatory action 
      via NF‑kappaB and AMPK‑dependent mechanisms.
FAU - Wang, Fei
AU  - Wang F
AD  - Health Management Institute, Chinese PLA General Hospital, Beijing 100853, P.R. 
      China.
FAU - Shang, Yanchang
AU  - Shang Y
AD  - Department of Geriatric Neurology, Chinese PLA General Hospital, Beijing 100853, 
      P.R. China.
FAU - Zhang, Rong
AU  - Zhang R
AD  - Health Management Institute, Chinese PLA General Hospital, Beijing 100853, P.R. 
      China.
FAU - Gao, Xiangyang
AU  - Gao X
AD  - Health Management Institute, Chinese PLA General Hospital, Beijing 100853, P.R. 
      China.
FAU - Zeng, Qiang
AU  - Zeng Q
AD  - Health Management Institute, Chinese PLA General Hospital, Beijing 100853, P.R. 
      China.
LA  - eng
PT  - Journal Article
DEP - 20181127
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Antioxidants)
RN  - 0 (HSP70 Heat-Shock Proteins)
RN  - 0 (Heterocyclic Compounds, 4 or More Rings)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (NF-kappa B)
RN  - 0 (Nfe2l2 protein, rat)
RN  - 0 (PPAR gamma)
RN  - 0 (SRT1720)
RN  - 5W494URQ81 (Streptozocin)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EC 1.14.13.39 (Nos3 protein, rat)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - EC 3.4.22.- (Casp3 protein, rat)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.5.1.- (Sirt1 protein, rat)
RN  - EC 3.5.1.- (Sirtuin 1)
SB  - IM
MH  - AMP-Activated Protein Kinases/genetics/metabolism
MH  - Animals
MH  - Anti-Inflammatory Agents/*pharmacology
MH  - Antioxidants/*pharmacology
MH  - Body Weight/drug effects
MH  - Caspase 3/genetics/metabolism
MH  - Cognitive Dysfunction/chemically induced/genetics/physiopathology/*prevention & 
      control
MH  - Diabetes Mellitus, Experimental/chemically induced/*drug 
      therapy/genetics/physiopathology
MH  - Gene Expression Regulation/drug effects
MH  - HSP70 Heat-Shock Proteins/genetics/metabolism
MH  - Heme Oxygenase-1/genetics/metabolism
MH  - Heterocyclic Compounds, 4 or More Rings/*pharmacology
MH  - Hippocampus/drug effects/metabolism/physiopathology
MH  - Hypoglycemic Agents/*pharmacology
MH  - Male
MH  - Maze Learning/drug effects
MH  - NF-E2-Related Factor 2/genetics/metabolism
MH  - NF-kappa B/genetics/metabolism
MH  - Nitric Oxide Synthase Type III/genetics/metabolism
MH  - PC12 Cells
MH  - PPAR gamma/genetics/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction
MH  - Sirtuin 1/genetics/metabolism
MH  - Streptozocin
MH  - Tissue Culture Techniques
PMC - PMC6323206
OTO - NOTNLM
OT  - sirtuin-1
OT  - cognitive decline
OT  - type 2 diabetic rats
OT  - nuclear factor-kappaB
OT  - AMP-activated protein kinase
EDAT- 2018/11/30 06:00
MHDA- 2019/05/28 06:00
PMCR- 2018/11/27
CRDT- 2018/11/29 06:00
PHST- 2017/10/08 00:00 [received]
PHST- 2018/03/02 00:00 [accepted]
PHST- 2018/11/30 06:00 [pubmed]
PHST- 2019/05/28 06:00 [medline]
PHST- 2018/11/29 06:00 [entrez]
PHST- 2018/11/27 00:00 [pmc-release]
AID - mmr-19-02-1040 [pii]
AID - 10.3892/mmr.2018.9699 [doi]
PST - ppublish
SO  - Mol Med Rep. 2019 Feb;19(2):1040-1048. doi: 10.3892/mmr.2018.9699. Epub 2018 Nov 
      27.