Phenolic antioxidants trolox and caffeic acid modulate the oxidized LDL-induced EGF-receptor activation

British Journal of Pharmacology
N VacaresseAnne Negre-Salvayre

Abstract

Oxidized low density lipoproteins (oxLDL) are thought to play a major role in atherosclerosis. OxLDL act in part through alteration of intracellular signalling pathways in cells of the vascular wall. We recently reported that the EGF receptor (EGFR) signalling pathway is activated by lipid peroxidation products (among them 4-hydroxynonenal, 4-HNE) contained in oxLDL. The use of phenolic antioxidants, such as trolox, alpha-tocopherol, caffeic acid and tyrphostins A-25, A-46 or A-1478, showed that the oxLDL-induced EGFR activation is constituted by two separate components, the first (early) one being antioxidant-insensitive, the second (late) being antioxidant-sensitive. 4-HNE derivatization of EGFR and EGFR activation induced by exogenous 4-HNE, suggest that the early (0.5 - 3 h) component of oxLDL-induced EGFR activation is mediated (at least in part) by 4-HNE (and possibly by other oxidized lipids). This early component is antioxidant-insensitive. The second component (4 - 5 h) of the oxLDL-induced EGFR activation is antioxidant-sensitive, since it is blocked by antioxidants such as trolox, caffeic acid or PDTC, which act by blocking the cellular oxidative stress (H(2)O(2) generation) evoked by oxLDL. Conversely, exogenous H(2...Continue Reading

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Citations

Aug 2, 2003·Molecular Aspects of Medicine·Anne Negre-SalvayreRobert Salvayre
Jan 18, 2003·Biochimica Et Biophysica Acta·Robert SalvayreAnne Negre-Salvayre
Sep 12, 2009·Circulation Research·Volker Rudolph, Bruce A Freeman
May 6, 2008·Free Radical Biology & Medicine·Yogesh C AwasthiSanjay Awasthi
Nov 6, 2004·Free Radical Biology & Medicine·Gabriella LeonarduzziGiuseppe Poli
Apr 30, 2002·Diabetes·Manuel Portero-OtínAnne Nègre-Salvayre
Dec 25, 2004·Arteriosclerosis, Thrombosis, and Vascular Biology·Cécile VindisRobert Salvayre
Dec 17, 2002·Arteriosclerosis, Thrombosis, and Vascular Biology·Nathalie AugeAnne Negre-Salvayre
Dec 7, 2007·Medicinal Research Reviews·G PoliG Leonarduzzi

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