期刊
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
卷 2018, 期 -, 页码 -出版社
HINDAWI LTD
DOI: 10.1155/2018/5852706
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资金
- Ministerio de Economia y Competitividad [SAF2010-22066-C02-01, SAF2010-22066-C02-02, SAF2011-28150, SAF2014-55523-R]
- Fondo Europeo de Desarrollo Regional (FEDER) [SAF2010-22066-C02-01, SAF2010-22066-C02-02, SAF2011-28150, SAF2014-55523-R]
- Junta de Andalucia (Proyecto de excelencia) [P12-CTS-2722]
- Instituto de Salud Carlos III, Spain [RIC RD12/0042/0011]
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) beta/delta 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 PPAR beta/delta agonists GW0742 and L165041. Both PPAR beta/delta 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 PPAR beta/delta agonists were reversed by either pharmacological inhibition or siRNA-based downregulation of PPAR beta/delta. These in vitro findings were confirmed in diabetic rats treated with GW0742. In conclusion, PPAR beta/delta 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, PPAR beta/delta activation could be of interest to prevent the progression of diabetic vascular complications.
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