Advanced Glycation End-Products and Hyperglycemia Increase Angiopoietin-2 Production by Impairing Angiopoietin-1-Tie-2 System.
Angiopoietin-1
/ metabolism
Angiopoietin-2
/ biosynthesis
Cell Line
Cell Proliferation
/ drug effects
Cell Survival
/ drug effects
Endothelial Cells
/ drug effects
Forkhead Box Protein O1
/ drug effects
Glucose
/ pharmacology
Glutathione
/ drug effects
Glycation End Products, Advanced
/ pharmacology
Humans
Hyperglycemia
/ metabolism
Phosphorylation
/ drug effects
Proto-Oncogene Proteins c-akt
/ drug effects
Reactive Oxygen Species
/ metabolism
Receptor, TIE-2
/ drug effects
Signal Transduction
Journal
Journal of diabetes research
ISSN: 2314-6753
Titre abrégé: J Diabetes Res
Pays: England
ID NLM: 101605237
Informations de publication
Date de publication:
2019
2019
Historique:
received:
11
07
2019
revised:
11
10
2019
accepted:
18
10
2019
entrez:
13
12
2019
pubmed:
13
12
2019
medline:
11
6
2020
Statut:
epublish
Résumé
The angiopoietin-Tie-2 system plays a crucial role in the maintenance of endothelial integrity. Hyperglycemia and advanced glycation end-products (AGEs) are involved in endothelial cell dysfunction responsible of the pathogenesis of microvascular complications of diabetes. Here, we investigated whether glycated serum (GS) or hyperglycemia (HG) affect the angiopoietin-Tie-2 system in the microvascular endothelial cells HMEC-1. We found that culture for 5 days in the presence of AGEs and HG (alone or in combination) decreased cell proliferation, increased reactive oxygen species (ROS) production, and reduced ratio between the oxidized and the reduced form of glutathione. Since angiopoietin-1 (Ang-1) signaling regulates angiopoietin-2 (Ang-2) expression through inactivation of the forkhead transcription factor FoxO1, we investigated intracellular signaling of Ang-1 and expression of Ang-2. HG and AGEs reduced phosphorylation of Akt and abrogated phosphorylation of FoxO1 induced by Ang-1 without affecting neither Tie-2 expression nor its activation. Furthermore, AGEs and/or HG induced nuclear translocation of FoxO1 and increased Ang-2 production. In conclusion, we demonstrated that both hyperglycemia and AGEs affect the angiopoietin-Tie-2 system by impairing Ang-1/Tie-2 signaling and by increasing Ang-2 expression. These results suggest that therapeutic strategies useful in preventing or delaying the onset of diabetic vascular complications should be aimed to preserve Ang-1 signaling.
Identifiants
pubmed: 31828164
doi: 10.1155/2019/6198495
pmc: PMC6881581
doi:
Substances chimiques
ANGPT1 protein, human
0
ANGPT2 protein, human
0
Angiopoietin-1
0
Angiopoietin-2
0
FOXO1 protein, human
0
Forkhead Box Protein O1
0
Glycation End Products, Advanced
0
Reactive Oxygen Species
0
Receptor, TIE-2
EC 2.7.10.1
TEK protein, human
EC 2.7.10.1
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
Glutathione
GAN16C9B8O
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
6198495Informations de copyright
Copyright © 2019 Alessandra Puddu et al.
Déclaration de conflit d'intérêts
The authors declare that there is no conflict of interest regarding the publication of this paper.
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