PMID- 32768436
OWN - NLM
STAT- MEDLINE
DCOM- 20210427
LR  - 20210427
IS  - 1873-6815 (Electronic)
IS  - 0531-5565 (Linking)
VI  - 139
DP  - 2020 Oct 1
TI  - Glucose restriction delays senescence and promotes proliferation of HUVECs via 
      the AMPK/SIRT1-FOXA3-Beclin1 pathway.
PG  - 111053
LID - S0531-5565(20)30401-0 [pii]
LID - 10.1016/j.exger.2020.111053 [doi]
AB  - Caloric restriction (CR) is an important means to delay senescence, and glucose 
      restriction is one of the measures to achieve CR. On the basis of our previous 
      work and bioinformatics analysis, we hypothesized that glucose restriction can 
      up-regulate autophagy, inhibit senescence and promote proliferation via the 
      AMPK/SIRT1-FOXA3-Beclin1 pathway in human umbilical vein endothelial cells 
      (HUVECs). We found that compared with 5.5 mmol/L and 25 mmol/L glucose, 
      2.5 mmol/L glucose restriction significantly reduced senescence, enhanced 
      autophagy, increased migration speed, relieved G(0)/G(1) phase arrest and 
      enhanced proliferation of HUVECs. Furthermore, glucose restriction up-regulated 
      AMPKalpha1, SIRT1, FOXA3 and Beclin1 expression in HUVECs. Additionally, we 
      demonstrated that AMPKalpha1 phosphorylated FOXA3 at S170 and S305 in the cytoplasm 
      and promoted FOXA3 nuclear translocation under glucose restriction. FOXA3 in the 
      nucleus was deacetylated by SIRT1 at K214 and K221. Deacetylated FOXA3 
      specifically bound to +109 C in the Beclin1 transcriptional regulatory region, 
      and significantly enhanced Beclin1 transcription and expression. siRNA knock down 
      of AMPKalpha1, SIRT1, FOXA3 or Beclin1 expression impaired the glucose 
      restriction-induced inhibition of senescence, enhanced autophagy, increased 
      migration, and induced proliferation of HUVECs. This study confirmed that glucose 
      restriction can enhance autophagy, inhibit senescence, and enhance proliferation 
      of HUVECs through the AMPK/SIRT1-FOXA3-Beclin1 pathway.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Liu, Qiang
AU  - Liu Q
AD  - Department of Gerontology, the Second Affiliated Hospital, Zhejiang University 
      School of Medicine, Hangzhou 310002, China. Electronic address: 
      liuqianghare@zju.edu.cn.
FAU - Li, Hong
AU  - Li H
AD  - Department of Cardiology, the Affiliated Hangzhou Hospital, Nanjing Medical 
      University, Hangzhou 310006, China.
FAU - Wang, Jing
AU  - Wang J
AD  - Department of Gerontology, the Second Affiliated Hospital, Zhejiang University 
      School of Medicine, Hangzhou 310002, China.
FAU - Zhong, Liang
AU  - Zhong L
AD  - Department of Gerontology, the Second Affiliated Hospital, Zhejiang University 
      School of Medicine, Hangzhou 310002, China.
FAU - Chen, Xian
AU  - Chen X
AD  - Department of Gerontology, the Second Affiliated Hospital, Zhejiang University 
      School of Medicine, Hangzhou 310002, China.
FAU - Zhang, Ruoyu
AU  - Zhang R
AD  - Department of Gerontology, the Second Affiliated Hospital, Zhejiang University 
      School of Medicine, Hangzhou 310002, China.
FAU - Wang, Hongping
AU  - Wang H
AD  - Department of Gerontology, the Second Affiliated Hospital, Zhejiang University 
      School of Medicine, Hangzhou 310002, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200805
PL  - England
TA  - Exp Gerontol
JT  - Experimental gerontology
JID - 0047061
RN  - 0 (Beclin-1)
RN  - 0 (FOXA3 protein, human)
RN  - 135845-91-9 (Hepatocyte Nuclear Factor 3-gamma)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - EC 3.5.1.- (SIRT1 protein, human)
RN  - EC 3.5.1.- (Sirtuin 1)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - *AMP-Activated Protein Kinases/genetics
MH  - Beclin-1/genetics
MH  - Cell Proliferation
MH  - Cellular Senescence
MH  - Glucose
MH  - Hepatocyte Nuclear Factor 3-gamma
MH  - Human Umbilical Vein Endothelial Cells
MH  - Humans
MH  - *Sirtuin 1/genetics
OTO - NOTNLM
OT  - Beclin1
OT  - Endothelial cells
OT  - FOXA3
OT  - Glucose restriction
OT  - Proliferation
OT  - Senescence
COIS- Declaration of competing interest None declared.
EDAT- 2020/08/10 06:00
MHDA- 2021/04/28 06:00
CRDT- 2020/08/10 06:00
PHST- 2020/01/08 00:00 [received]
PHST- 2020/07/07 00:00 [revised]
PHST- 2020/08/01 00:00 [accepted]
PHST- 2020/08/10 06:00 [pubmed]
PHST- 2021/04/28 06:00 [medline]
PHST- 2020/08/10 06:00 [entrez]
AID - S0531-5565(20)30401-0 [pii]
AID - 10.1016/j.exger.2020.111053 [doi]
PST - ppublish
SO  - Exp Gerontol. 2020 Oct 1;139:111053. doi: 10.1016/j.exger.2020.111053. Epub 2020 
      Aug 5.