RT info:eu-repo/semantics/article T1 Modulation of Akt-p38-MAPK/Nrf2/SIRT1 and NF-κB pathways by wine pomace product in hyperglycemic endothelial cell line A1 Gerardi, Gisela A1 Cavia Saiz, Mónica A1 Rivero Pérez, Maria Dolores A1 González San José, Mª Luisa A1 Muñiz Rodríguez, Pilar K1 Polyphenols K1 Wine pomace K1 Endothelial dysfunction K1 NF-κB K1 Nrf2 K1 p38MAPK K1 Akt K1 SIRT1 K1 Oxidative stress K1 EA.hy926 K1 Phase 2 enzymes K1 SOD2 K1 NOX4 K1 COX2 K1 Alimentos K1 Food K1 Bioquímica K1 Biochemistry K1 Biología molecular K1 Molecular biology AB Wine by-products show great potential as source of bioactive compounds that protect the vascular endothelial function by the modulation of both Nrf2 and Nf-κB pathways. This study investigates the pathways involved in the effects of a red wine pomace product (rWPP) against inflammatory and oxidative damage in hyperglycemic EA.hy926 endothelial cells. rWPP-digested fractions showed an inhibitory effect on IKK/IκBα/NF-κB pathway and a stimulatory effect on Akt-p38-MAPK/Nrf2 pathway with an impact on their antioxidant and anti-inflammatory downstream targets. In addition, the pathways regulation was also accompanied by downregulation of the gene expression of superoxide dismutase 2, cyclooxygenase 2 and NADPH oxidase 4. These results suggest the expression of SOD2 as an early adaptive response to the inflammatory effect mediated by NF-κB in hyperglycemic cells, and the treatment with the rWPP-digested fractions regulate this inflammatory process by Nrf2 pathway increased expression of antioxidant enzymes. PB Elsevier SN 1756-4646 YR 2019 FD 2019-07 LK http://hdl.handle.net/10259/8054 UL http://hdl.handle.net/10259/8054 LA spa NO The authors thank the financial support of the Autonomous Government of Castilla y León (Research project BU282U13). DS Repositorio Institucional de la Universidad de Burgos RD 10-may-2024