Modulation of oxidative stress and tau phosphorylation by the mTOR activator phosphatidic acid in SH-SY5Y cells |
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Authors: | Taga Mariko Mouton-Liger François Paquet Claire Hugon Jacques |
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Institution: | 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 |
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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. |
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