@misc{10481/56303,
year = {2018},
month = {7},
url = {http://hdl.handle.net/10481/56303},
abstract = {Hyperglycemia induces oxidative stress and plays a substantial role in the progression of vascular diseases. Here, we demonstrated the potentiality of peroxisome proliferator-activated receptor (PPAR)β/δ activation in attenuating high glucose-induced oxidative stress in endothelial cells and diabetic rats, pointing to the involvement of nuclear factor erythroid 2-related factor 2 (Nrf2). HUVECs exposed to high glucose showed increased levels of reactive oxygen species (ROS) and upregulated NOX-2, NOX-4, Nrf2, and NQO-1 effects that were significantly reversed by the PPARβ/δ agonists GW0742 and L165041. Both PPARβ/δ agonists, in a concentration-dependent manner, induced transcriptional and protein upregulation of heme oxygenase-1 (HO-1) under low- and high-glucose conditions. All effects of PPARβ/δ agonists were reversed by either pharmacological inhibition or siRNA-based downregulation of PPARβ/δ. These in vitro findings were confirmed in diabetic rats treated with GW0742. In conclusion, PPARβ/δ activation confers vascular protection against hyperglycemia-induced oxidative stress by suppressing NOX-2 and NOX-4 expression plus a direct induction of HO-1; with the subsequent downregulation of the Nrf2 pathway. Thus, PPARβ/δ activation could be of interest to prevent the progression of diabetic vascular complications.},
organization = {This work was supported by Grants from Ministerio de Economía y Competitividad and Fondo Europeo de Desar- rollo Regional (FEDER) (SAF2010-22066-C02-01, SAF2010-22066-C02-02, SAF2011-28150, SAF2014-55523- R), Junta de Andalucía (Proyecto de excelencia, P12-CTS- 2722), and Instituto de Salud Carlos III (RIC RD12/0042/ 0011), Spain.},
publisher = {Hindawi},
keywords = {Nrf2},
keywords = {PPAR},
keywords = {Hyperglycemia},
keywords = {Diabetes},
keywords = {Oxidative Stress},
keywords = {HUVECs},
title = {The Role of Nrf2 Signaling in PPARβ/δ-Mediated Vascular Protection against Hyperglycemia-Induced Oxidative Stress},
doi = {10.1155/2018/5852706},
author = {Jiménez, Rosario and Toral Jiménez, Marta and Gómez Guzmán, Manuel and Romero Pérez, Miguel and Sánchez, Manuel and Mahmoud, Ayman M. and Duarte, Juan},
}