title: Modulation of oxidative stress and tau phosphorylation by the mTOR activator phosphatidic acid in SH-SY5Y cells.
abstract: The mammalian target of rapamycin complex 1 (mTORC1) pathway including p70(S6K) (the 70-kDa p70 S6 kinase) and S6, controls protein synthesis, has anti-apoptotic functions and can phosphorylate tau protein. mTORC1 is triggered by nutrients such as phosphatidic acid (PA). Previous experimental studies have shown that oxidative stress may down-regulate this pathway leading to neuronal death. Our results showed that in human neuroblastoma cells, PA exposure can reduce H(2)O(2)-induced apoptosis and can increase tau protein phosphorylation on Ser214 via p70(S6K) activation. These findings reveal that PA, via the mTOR kinase, can trigger tau phosphorylation on a site known to reduce paired helical filament (PHF) formation.
authors.affiliation: Centre Mémoire de Ressources et de Recherche (CMRR), Groupe Hospitalier Lariboisière, Fernand Widal, Saint-Louis AP-HP, Université Paris VII, Paris, France. mariko.taga@inserm.fr
authors.forename: Mariko
authors.initials: M
authors.lastname: Taga
authors.forename: François
authors.initials: F
authors.lastname: Mouton-Liger
authors.forename: Claire
authors.initials: C
authors.lastname: Paquet
authors.forename: Jacques
authors.initials: J
authors.lastname: Hugon
mesh_terms: D045744:Cell Line, Tumor; D006801:Humans; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology*; D018384:Oxidative Stress; D010712:Phosphatidic Acids / Q000502:physiology*; D010766:Phosphorylation; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism*
chemical_list: C054369:MAPT protein, human; D010712:Phosphatidic Acids; D016875:tau Proteins; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases