title: Hydroxytyrosol attenuates tunicamycin-induced endoplasmic reticulum stress in human hepatocarcinoma cells.
abstract: METHODS
  Hydroxytyrosol (HT) is a phenolic compound peculiarly abundant in olives and it is being recognized as a protector of LDL from oxidation. In addition to lipid oxidation, one emerging risk factor for cardiovascular disease is ER stress. We tested the effect of HT on the modulation of ER stress in HepG2 cells.
  
  
  RESULTS
  HepG2 cells were treated with 1 μM and 5 μM of HT and 100 μM lipoic acid (LA) and glutathione-ethyl ester (GSH), for 24 h. Induction of the unfolded protein response (UPR) was initiated by treatment with 2 μg/mL tunicamycin for 4 h. Real time RT-PCR analyses followed by Western blot and ELISA of different ER stress markers revealed that the protective activities of HT were superior to those of two known thiolic antioxidants, i.e., LA and GSH.
  
  
  CONCLUSIONS
  Mounting evidence indicates the ER as an important target of dietary or pharmacological intervention. In this paper, we report the modulatory activities of physiological concentrations of HT toward ER stress and we shed some light on pathways alternative to the well-known antioxidant mechanisms, through which olive oil phenolics modulate cell signaling and could impact cardiovascular health and degenerative diseases.
authors.affiliation: Laboratory of Functional Foods, Madrid Institute for Advanced Studies (IMDEA)-Food, CEI UAM + CSIC, Madrid, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Giordano
authors.forename: Alberto
authors.initials: A
authors.lastname: Davalos
authors.forename: Nathalie
authors.initials: N
authors.lastname: Nicod
authors.forename: Francesco
authors.initials: F
authors.lastname: Visioli
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005978:Glutathione / Q000031:analogs & derivatives / Q000494:pharmacology; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D031658:Olea / Q000737:chemistry; D000069463:Olive Oil; D010636:Phenols / Q000494:pharmacology; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology; D010938:Plant Oils / Q000737:chemistry; D012307:Risk Factors; D015398:Signal Transduction; D008063:Thioctic Acid / Q000494:pharmacology; D014415:Tunicamycin / Q000009:adverse effects*; D056811:Unfolded Protein Response
chemical_list: D000975:Antioxidants; D000069463:Olive Oil; D010636:Phenols; D010936:Plant Extracts; D010938:Plant Oils; C005975:3,4-dihydroxyphenylethanol; D014415:Tunicamycin; D008063:Thioctic Acid; C042431:S-ethyl glutathione; D005978:Glutathione; D010626:Phenylethyl Alcohol
keywords: Antioxidants; ER stress; Hydroxytyrosol; Mediterranean diet; Polyphenols