PMID- 25162034
OWN - NLM
STAT- MEDLINE
DCOM- 20150526
LR  - 20220311
IS  - 2314-6141 (Electronic)
IS  - 2314-6133 (Print)
VI  - 2014
DP  - 2014
TI  - Oxidative stress induces endothelial cell senescence via downregulation of Sirt6.
PG  - 902842
LID - 10.1155/2014/902842 [doi]
LID - 902842
AB  - Accumulating evidence has shown that diabetes accelerates aging and endothelial 
      cell senescence is involved in the pathogenesis of diabetic vascular 
      complications, including diabetic retinopathy. Oxidative stress is recognized as 
      a key factor in the induction of endothelial senescence and diabetic retinopathy. 
      However, specific mechanisms involved in oxidative stress-induced endothelial 
      senescence have not been elucidated. We hypothesized that Sirt6, which is a 
      nuclear, chromatin-bound protein critically involved in many pathophysiologic 
      processes such as aging and inflammation, may have a role in oxidative 
      stress-induced vascular cell senescence. Measurement of Sirt6 expression in human 
      endothelial cells revealed that H2O2 treatment significantly reduced Sirt6 
      protein. The loss of Sirt6 was associated with an induction of a senescence 
      phenotype in endothelial cells, including decreased cell growth, proliferation 
      and angiogenic ability, and increased expression of senescence-associated 
      beta-galactosidase activity. Additionally, H2O2 treatment reduced eNOS expression, 
      enhanced p21 expression, and dephosphorylated (activated) retinoblastoma (Rb) 
      protein. All of these alternations were attenuated by overexpression of Sirt6, 
      while partial knockdown of Sirt6 expression by siRNA mimicked the effect of H2O2. 
      In conclusion, these results suggest that Sirt6 is a critical regulator of 
      endothelial senescence and oxidative stress-induced downregulation of Sirt6 is 
      likely involved in the pathogenesis of diabetic retinopathy.
FAU - Liu, Rong
AU  - Liu R
AD  - Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan 430030, China ; Department of 
      Ophthalmology and Visual Sciences, The University of Texas Medical Branch, 301 
      University Boulevard, Galveston, TX 77555, USA.
FAU - Liu, Hua
AU  - Liu H
AUID- ORCID: 0000-0003-2798-3337
AD  - Center for Biomedical Engineering, The University of Texas Medical Branch, 
      Galveston, TX, USA.
FAU - Ha, Yonju
AU  - Ha Y
AUID- ORCID: 0000-0001-9622-8410
AD  - Department of Ophthalmology and Visual Sciences, The University of Texas Medical 
      Branch, 301 University Boulevard, Galveston, TX 77555, USA.
FAU - Tilton, Ronald G
AU  - Tilton RG
AD  - Department of Ophthalmology and Visual Sciences, The University of Texas Medical 
      Branch, 301 University Boulevard, Galveston, TX 77555, USA ; Internal Medicine, 
      Division of Endocrinology and Stark Diabetes Center, The University of Texas 
      Medical Branch, Galveston, TX, USA.
FAU - Zhang, Wenbo
AU  - Zhang W
AUID- ORCID: 0000-0002-8694-2554
AD  - Department of Ophthalmology and Visual Sciences, The University of Texas Medical 
      Branch, 301 University Boulevard, Galveston, TX 77555, USA ; Center for 
      Biomedical Engineering, The University of Texas Medical Branch, Galveston, TX, 
      USA ; Neuroscience and Cell Biology, The University of Texas Medical Branch, 
      Galveston, TX, USA.
LA  - eng
GR  - R01 EY022694/EY/NEI NIH HHS/United States
GR  - EY022694/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20140805
PL  - United States
TA  - Biomed Res Int
JT  - BioMed research international
JID - 101600173
RN  - 0 (RNA, Small Interfering)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 1.14.13.39 (NOS3 protein, human)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EC 3.5.1.- (SIRT6 protein, human)
RN  - EC 3.5.1.- (Sirtuins)
SB  - IM
MH  - Cellular Senescence/*drug effects/genetics
MH  - Diabetic Retinopathy/*genetics/pathology
MH  - Endothelial Cells/metabolism/pathology
MH  - Gene Expression Regulation/drug effects
MH  - Humans
MH  - Hydrogen Peroxide/administration & dosage
MH  - Nitric Oxide Synthase Type III/biosynthesis
MH  - Oxidative Stress/*genetics
MH  - RNA, Small Interfering
MH  - Sirtuins/*biosynthesis/genetics
PMC - PMC4138737
EDAT- 2014/08/28 06:00
MHDA- 2015/05/27 06:00
PMCR- 2014/08/05
CRDT- 2014/08/28 06:00
PHST- 2014/06/15 00:00 [received]
PHST- 2014/07/13 00:00 [accepted]
PHST- 2014/08/28 06:00 [entrez]
PHST- 2014/08/28 06:00 [pubmed]
PHST- 2015/05/27 06:00 [medline]
PHST- 2014/08/05 00:00 [pmc-release]
AID - 10.1155/2014/902842 [doi]
PST - ppublish
SO  - Biomed Res Int. 2014;2014:902842. doi: 10.1155/2014/902842. Epub 2014 Aug 5.