title: Protocatechuic Acid Prevents oxLDL-Induced Apoptosis by Activating JNK/Nrf2 Survival Signals in Macrophages.
abstract: Protocatechuic acid (PCA), one of the main metabolites of complex polyphenols, exerts numerous biological activities including antiapoptotic, anti-inflammatory, and antiatherosclerotic effects. Oxidised LDL have atherogenic properties by damaging arterial wall cells and inducing p53-dependent apoptosis in macrophages. This study was aimed at defining the molecular mechanism responsible for the protective effects of PCA against oxidative and proapoptotic damage exerted by oxLDL in J774 A.1 macrophages. We found that the presence of PCA in cells treated with oxLDL completely inhibited the p53-dependent apoptosis induced by oxLDL. PCA decreased oxLDL-induced ROS overproduction and in particular prevented the early increase of ROS. This decrease seemed to be the main signal responsible for maintaining the intracellular redox homeostasis hindering the activation of p53 induced by ROS, p38MAPK, and PKCδ. Consequently the overexpression of the proapoptotic p53-target genes such as p66Shc protein did not occur. Finally, we demonstrated that PCA induced the activation of JNK, which, in turn, determined the increase of nuclear Nrf2, leading to inhibition of the early ROS overproduction. We concluded that the antiapoptotic mechanism of PCA was most likely related to the activation of the JNK-mediated survival signals that strengthen the cellular antioxidant defences rather than to the PCA antioxidant power.
authors.affiliation: Department of Veterinary Public Health and Food Safety, Nutrition Unit, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Rosaria
authors.initials: R
authors.lastname: Varì
authors.affiliation: Department of Veterinary Public Health and Food Safety, Nutrition Unit, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Scazzocchio
authors.affiliation: Department of Veterinary Public Health and Food Safety, Nutrition Unit, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Santangelo
authors.affiliation: Department of Veterinary Public Health and Food Safety, Nutrition Unit, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Carmelina
authors.initials: C
authors.lastname: Filesi
authors.affiliation: Department of Clinical and Molecular Biomedicine, Section of Pharmacology and Biochemistry, University of Catania, Viale A. Doria 6, 95125 Catania, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Galvano
authors.affiliation: Department of Veterinary Public Health and Food Safety, Nutrition Unit, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: D'Archivio
authors.affiliation: Department of Veterinary Public Health and Food Safety, Nutrition Unit, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Masella
authors.affiliation: Department of Veterinary Public Health and Food Safety, Nutrition Unit, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Giovannini
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D062385:Hydroxybenzoates / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000633:toxicity*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D051745:Protein Kinase C-delta / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D062385:Hydroxybenzoates; D008077:Lipoproteins, LDL; D051267:NF-E2-Related Factor 2; D017382:Reactive Oxygen Species; C099252:oxidized low density lipoprotein; C009091:protocatechuic acid; C497259:Prkcd protein, mouse; D051745:Protein Kinase C-delta; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases