title: Nonenzymatic oxygenated metabolites of α-linolenic acid B1- and L1-phytoprostanes protect immature neurons from oxidant injury and promote differentiation of oligodendrocyte progenitors through PPAR-γ activation.
abstract: Phytoprostanes (PhytoP's) are formed in higher plants from α-linolenic acid via a nonenzymatic free radical-catalyzed pathway and act as endogenous mediators capable of protecting cells from damage under various conditions related to oxidative stress. Humans are exposed to PhytoP's, as they are present in relevant quantities in vegetable food and pollen. The uptake of PhytoP's through the olfactory epithelium of the nasal mucosa, upon pollen grain inhalation, is of interest as the intranasal pathway is regarded as a direct route of communication between the environment and the brain. On this basis, we sought to investigate the potential activities of PhytoP's on immature cells of the central nervous system, which are particularly susceptible to oxidative stress. In neuroblastoma SH-SY5Y cells, used as a model for undifferentiated neurons, B1-PhytoP's, but not F1-PhytoP's, increased cell metabolic activity and protected them from oxidant damage caused by H2O2. Moreover, B1-PhytoP's induced a moderate depolarization of the mitochondrial inner membrane potential. These effects were prevented by the PPAR-γ antagonist GW9662. When SH-SY5Y cells were induced to differentiate toward a more mature phenotype, they became resistant to B1-PhytoP activities. B1-PhytoP's also influenced immature cells of an oligodendroglial line, as they increased the metabolic activity of oligodendrocyte progenitors and strongly accelerated their differentiation to immature oligodendrocytes, through mechanisms at least partially dependent on PPAR-γ activity. However, B1-PhytoP's did not protect oligodendrocyte progenitors against oxidant injury. Taken together, these data suggest that B1-PhytoP's, through novel mechanisms involving PPAR-γ, can specifically affect immature brain cells, such as neuroblasts and oligodendrocyte progenitors, thereby conferring neuroprotection against oxidant injury and promoting myelination.
authors.affiliation: Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, 00161 Rome, Italy. Electronic address: luisa.minghetti@iss.it.
authors.forename: Luisa
authors.initials: L
authors.lastname: Minghetti
authors.affiliation: Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, 00161 Rome, Italy.
authors.forename: Rachele
authors.initials: R
authors.lastname: Salvi
authors.affiliation: Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, 00161 Rome, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Lavinia Salvatori
authors.affiliation: Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, 00161 Rome, Italy.
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Ajmone-Cat
authors.affiliation: Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, 00161 Rome, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: De Nuccio
authors.affiliation: Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, 00161 Rome, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Visentin
authors.affiliation: Institut des Biomolécules Max Mousseron, UMR 5247 CNRS, UM I, UM II, ENSCM, Montpellier, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Bultel-Poncé
authors.affiliation: Institut des Biomolécules Max Mousseron, UMR 5247 CNRS, UM I, UM II, ENSCM, Montpellier, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Oger
authors.affiliation: Institut des Biomolécules Max Mousseron, UMR 5247 CNRS, UM I, UM II, ENSCM, Montpellier, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Guy
authors.affiliation: Institut des Biomolécules Max Mousseron, UMR 5247 CNRS, UM I, UM II, ENSCM, Montpellier, France.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Galano
authors.affiliation: Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, 00161 Rome, Italy.
authors.forename: Anita
authors.initials: A
authors.lastname: Greco
authors.affiliation: Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, 00161 Rome, Italy.
authors.forename: Antonietta
authors.initials: A
authors.lastname: Bernardo
authors.affiliation: Institut des Biomolécules Max Mousseron, UMR 5247 CNRS, UM I, UM II, ENSCM, Montpellier, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Durand
mesh_terms: D000813:Anilides / Q000494:pharmacology; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002490:Central Nervous System / Q000166:cytology; D003517:Cyclopentanes / Q000494:pharmacology*; D004789:Enzyme Activation; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005663:Furans / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D058953:Neural Stem Cells / Q000166:cytology*; D009474:Neurons / Q000166:cytology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009836:Oligodendroglia / Q000166:cytology; D018384:Oxidative Stress; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017962:alpha-Linolenic Acid / Q000378:metabolism
chemical_list: C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D003517:Cyclopentanes; D005231:Fatty Acids, Unsaturated; D005663:Furans; D018696:Neuroprotective Agents; D047495:PPAR gamma; C500684:phytoprostane B1 type I; C486066:phytoprostane F1; D017962:alpha-Linolenic Acid; D006861:Hydrogen Peroxide
keywords: Fatty acids; Free radicals; Myelin; Neuroblasts; Neuroprotection; Oligodendrocytes; Oxidative stress; Progenitors