Modulation of Akt-p38-MAPK/Nrf2/SIRT1 and NF-κB pathways by wine pomace product in hyperglycemic endothelial cell line

• Published in: Journal of functional foods Vol. 58; pp. 255 - 265
• Main Authors: Gerardi, Gisela, Cavia-Saiz, Mónica, Rivero-Pérez, María D., González-SanJosé, María L., Muñiz, Pilar
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.07.2019; Elsevier
• Subjects: Akt; COX2; EA.hy926; Endothelial dysfunction; NF-κB; NOX4; Nrf2; Oxidative stress; p38 MAPK; Phase 2 enzymes; Polyphenols; SIRT1; SOD2; Wine pomace; Oxidative stress; NO; eNOS; Phase 2 enzymes; Wine pomace; p38-MAPK; HO1; WPF; rWPP; NF-κB; WPGI; PI3K; Nrf2; Polyphenols; Endothelial dysfunction; COX2; GSH; AREs; GSSG; NQO1; GPX1; IKK; Akt; GR; EA.hy926; SOD2; GS; p38 MAPK; SIRT1; IκBα; SOD1; GCLC; CAT; ROS; NOX4; GAPDH
• ISSN: 1756-4646; 2214-9414
• DOI: 10.1016/j.jff.2019.05.003

[Display omitted] •Hyperglycemic-induced oxidative stress upregulates NF-κB and downregulate Nrf2 pathways.•NF-κB/SOD2 participates in an early adaptive response to oxidative stress.•rWPP reduce endothelial oxidative stress through Nrf2, SIRT1 and NF-κB.•rWPP increases antioxidant and antiinflamatory cell response. 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.