Establishment of pancreatic microenvironment model of ER stress: Quercetin attenuates ß-cell apoptosis by invoking nitric oxide-cGMP signaling in endothelial cells.
J Nutr Biochem
; 55: 142-156, 2018 05.
Article
em En
| MEDLINE
| ID: mdl-29455095
ABSTRACT
The involvement of endoplasmic reticulum (ER) stress in endothelial dysfunction and diabetes-associated complications has been well documented. Inhibition of ER stress represents a promising therapeutic strategy to attenuate endothelial dysfunction in diabetes. Recent attention has focused on the development of small molecule inhibitors of ER stress to maintain endothelial homeostasis in diabetes. Here we have developed a reliable, robust co-culture system that allows a study on the endothelial cells and pancreatic ß-cells crosstalk under ER stress and validated using a known ER stress modulator, quercetin. Furthermore, sensitizing of endothelial cells by quercetin (25 µM) confers protection of pancreatic ß-cells against ER stress through nitric oxide (NOâ) signaling. In addition, increased intracellular insulin and NOâ-mediated cyclic 3',5'-guanosine monophosphate (cGMP) levels in pancreatic ß-cells further confirmed the mechanism of protection under co-culture system. In addition, the potential protein targets of quercetin against ER stress in the endothelial cells were investigated through proteomic profiling and its phosphoprotein targets through Bioplex analysis. On the whole, the developed in vitro co-culture set up can serve as a platform to study the signaling network between the endothelial and pancreatic ß-cells as well as provides a mechanistic insight for the validation of novel ER stress modulators.
Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Quercetina
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GMP Cíclico
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Células Secretoras de Insulina
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Estresse do Retículo Endoplasmático
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Óxido Nítrico
Limite:
Animals
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article