Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Vacaresse, N; Vieira, O; Robbesyn, F; Jürgens, G; Salvayre, R; Negre-Salvayre, A.
Phenolic antioxidants trolox and caffeic acid modulate the oxidized LDL-induced EGF-receptor activation.
Br J Pharmacol. 2001; 132(8):1777-1788
Doi: 10.1038/sj.bjp.0703981
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- Co-Autor*innen der Med Uni Graz
- Jürgens Günther
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- 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)O(2) induced EGFR autophosphorylation (thus mimicking the second component) and was also inhibited by antioxidants. This effect is mediated in part through inhibition by oxidative stress of protein tyrosine phosphatases involved in EGFR dephosphorylation.
- Find related publications in this database (using NLM MeSH Indexing)
- Aldehydes - pharmacology
- Antioxidants - pharmacology
- Biotransformation - drug effects
- Blotting, Western - drug effects
- Caffeic Acids - pharmacology
- Cell Line - pharmacology
- Chromans - pharmacology
- Cross-Linking Reagents - pharmacology
- Humans - pharmacology
- Hydrogen Peroxide - pharmacology
- Lipoproteins, LDL - antagonists and inhibitors
- Oxidation-Reduction - antagonists and inhibitors
- Phosphorylation - antagonists and inhibitors
- Precipitin Tests - antagonists and inhibitors
- Protein-Tyrosine Kinases - metabolism
- Protein-Tyrosine-Phosphatase - antagonists and inhibitors
- Receptor, Epidermal Growth Factor - drug effects
- Find related publications in this database (Keywords)
- oxidized LDL
- EGF-receptor
- 4-hydroxynonenal
- tyrosine phosphorylation
- caffeic acid
- trolox
- antioxidants
- atherosclerosis