Quercetin alleviates high glucose-induced damage on human umbilical vein endothelial cells by promoting autophagy.
Adenine
/ analogs & derivatives
Antioxidants
/ pharmacology
Autophagy
/ drug effects
Beclin-1
/ metabolism
Cell Movement
/ drug effects
Cell Survival
/ drug effects
Cytoprotection
/ drug effects
Glucose
/ adverse effects
Human Umbilical Vein Endothelial Cells
/ drug effects
Humans
Microtubule-Associated Proteins
/ metabolism
Oxidative Stress
/ drug effects
Quercetin
/ pharmacology
RNA-Binding Proteins
/ metabolism
Reactive Oxygen Species
/ metabolism
Autophagy status
Diabetic condition
Human umbilical vein endothelial cells
Quercetin
Journal
Phytomedicine : international journal of phytotherapy and phytopharmacology
ISSN: 1618-095X
Titre abrégé: Phytomedicine
Pays: Germany
ID NLM: 9438794
Informations de publication
Date de publication:
15 Mar 2019
15 Mar 2019
Historique:
received:
31
07
2018
revised:
08
10
2018
accepted:
07
11
2018
pubmed:
23
1
2019
medline:
22
5
2019
entrez:
23
1
2019
Statut:
ppublish
Résumé
Quercetin, a flavonoid antioxidant, has been found to exert therapeutic effects in diabetic condition. Autophagy represents a homeostatic cellular mechanism for the turnover of unfolds proteins and damaged organelles through a lysosome-dependent degradation manner. We speculated that quercetin could protect endothelial cells against high glucose-induced damage by promoting autophagic responses. HUVECs viability was evaluated by MTT method. Griess and TBARS assays were used to monitor the levels of NO and MDA, respectively. Intracellular ROS generation was determined in DCFDA-stained cells analyzed by flow cytometry. To investigate the role of quercetin in endothelial cell migratory behavior, we used a scratch test. The level of autophagy proteins LC3, Beclin-1 and P62 were measured by western blotting technique. Our results showed that quercetin had the potential to increase cell survival after exposure to high glucose (P < 0.05). Total levels of oxidative stress markers were profoundly decreased and the activity of GSH was increased by quercetin (P < 0.05). High glucose suppressed HUVECs migration to the scratched area (P < 0.05). However, a significant stimulation in cell migration was observed after exposure to quercetin (P < 0.05). Based on data, autophagy was blocked at the late stage by high glucose concentration while quercetin enhanced autophagic response by reducing the P62 level coincided with the induction of Beclin-1 and LC3-II to LC3-I ratio (P < 0.05). All these beneficial effects were reversed by 3-methyladenine as an autophagy inhibitor. Together, our data suggest that quercetin could protect HUVECs from high glucose induced-damage possibly by activation of the autophagy response.
Sections du résumé
BACKGROUND
BACKGROUND
Quercetin, a flavonoid antioxidant, has been found to exert therapeutic effects in diabetic condition. Autophagy represents a homeostatic cellular mechanism for the turnover of unfolds proteins and damaged organelles through a lysosome-dependent degradation manner. We speculated that quercetin could protect endothelial cells against high glucose-induced damage by promoting autophagic responses.
METHODS
METHODS
HUVECs viability was evaluated by MTT method. Griess and TBARS assays were used to monitor the levels of NO and MDA, respectively. Intracellular ROS generation was determined in DCFDA-stained cells analyzed by flow cytometry. To investigate the role of quercetin in endothelial cell migratory behavior, we used a scratch test. The level of autophagy proteins LC3, Beclin-1 and P62 were measured by western blotting technique.
RESULTS
RESULTS
Our results showed that quercetin had the potential to increase cell survival after exposure to high glucose (P < 0.05). Total levels of oxidative stress markers were profoundly decreased and the activity of GSH was increased by quercetin (P < 0.05). High glucose suppressed HUVECs migration to the scratched area (P < 0.05). However, a significant stimulation in cell migration was observed after exposure to quercetin (P < 0.05). Based on data, autophagy was blocked at the late stage by high glucose concentration while quercetin enhanced autophagic response by reducing the P62 level coincided with the induction of Beclin-1 and LC3-II to LC3-I ratio (P < 0.05). All these beneficial effects were reversed by 3-methyladenine as an autophagy inhibitor.
CONCLUSION
CONCLUSIONS
Together, our data suggest that quercetin could protect HUVECs from high glucose induced-damage possibly by activation of the autophagy response.
Identifiants
pubmed: 30668339
pii: S0944-7113(18)30565-8
doi: 10.1016/j.phymed.2018.11.008
pii:
doi:
Substances chimiques
Antioxidants
0
BECN1 protein, human
0
Beclin-1
0
MAP1LC3A protein, human
0
Microtubule-Associated Proteins
0
P62 protein, human
0
RNA-Binding Proteins
0
Reactive Oxygen Species
0
3-methyladenine
5142-23-4
Quercetin
9IKM0I5T1E
Glucose
IY9XDZ35W2
Adenine
JAC85A2161
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
183-193Informations de copyright
Copyright © 2018. Published by Elsevier GmbH.