Oxidative Stress Induces Endothelial Cell Senescence via Downregulation of Sirt6
Joint Authors
Liu, Hua
Tilton, Ronald G.
Liu, Rong
Ha, Yonju
Zhang, Wenbo
Source
Issue
Vol. 2014, Issue 2014 (31 Dec. 2014), pp.1-13, 13 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2014-08-05
Country of Publication
Egypt
No. of Pages
13
Main Subjects
Abstract EN
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 β-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.
American Psychological Association (APA)
Liu, Rong& Liu, Hua& Ha, Yonju& Tilton, Ronald G.& Zhang, Wenbo. 2014. Oxidative Stress Induces Endothelial Cell Senescence via Downregulation of Sirt6. BioMed Research International،Vol. 2014, no. 2014, pp.1-13.
https://search.emarefa.net/detail/BIM-506684
Modern Language Association (MLA)
Liu, Rong…[et al.]. Oxidative Stress Induces Endothelial Cell Senescence via Downregulation of Sirt6. BioMed Research International No. 2014 (2014), pp.1-13.
https://search.emarefa.net/detail/BIM-506684
American Medical Association (AMA)
Liu, Rong& Liu, Hua& Ha, Yonju& Tilton, Ronald G.& Zhang, Wenbo. Oxidative Stress Induces Endothelial Cell Senescence via Downregulation of Sirt6. BioMed Research International. 2014. Vol. 2014, no. 2014, pp.1-13.
https://search.emarefa.net/detail/BIM-506684
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-506684