title: Involvement of ERK, Akt and JNK signalling in H2O2-induced cell injury and protection by hydroxytyrosol and its metabolite homovanillic alcohol.
abstract: The olive oil polyphenol, hydroxytyrosol (HT), is believed to be capable of exerting protection against oxidative kidney injury. In this study we have investigated the ability of HT and its O-methylated metabolite, homovanillic alcohol (HVA) to protect renal cells against oxidative damage induced by hydrogen peroxide. We show that both compounds were capable of inhibiting hydrogen peroxide-induced kidney cell injury via an ability to interact with both MAP kinase and PI3 kinase signalling pathways, albeit at different concentrations. HT strongly inhibited death and prevented peroxide-induced increases in ERK1/2 and JNK1/2/3 phosphorylation at 0.3 microM, whilst HVA was effective at 10 microM. At similar concentrations, both compounds also prevented peroxide-induced reductions in Akt phosphorylation. We suggest that one potential protective effect exerted by olive oil polyphenols against oxidative kidney cell injury may be attributed to the interactions of HT and HVA with these important intracellular signalling pathways.
authors.affiliation: Molecular Nutrition Group, School of Chemistry, Food and Pharmacy, University of Reading, Whiteknights, Reading, UK.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Incani
authors.forename: Monica
authors.initials: M
authors.lastname: Deiana
authors.forename: Giulia
authors.initials: G
authors.lastname: Corona
authors.forename: Katerina
authors.initials: K
authors.lastname: Vafeiadou
authors.forename: David
authors.initials: D
authors.lastname: Vauzour
authors.forename: M Assunta
authors.initials: MA
authors.lastname: Dessì
authors.forename: Jeremy P E
authors.initials: JP
authors.lastname: Spencer
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019610:Cytoprotection; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology*; D006719:Homovanillic Acid / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000633:toxicity*; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology*; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects*; D013552:Swine
chemical_list: C532664:homovanillic alcohol; C005975:3,4-dihydroxyphenylethanol; D006861:Hydrogen Peroxide; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D010626:Phenylethyl Alcohol; D006719:Homovanillic Acid