title: Citicoline increases glutathione redox ratio and reduces caspase-3 activation and cell death in staurosporine-treated SH-SY5Y human neuroblastoma cells.
abstract: Citicoline, or CDP-choline, is an essential endogenous intermediate in the biosynthesis of phosphatidylcholine that may act as a neuroprotector in several models of neurodegeneration. The present study analyses the effects of citicoline in the paradigm of staurosporine-induced cell death in human SH-SY5Y neuroblastoma cells. Citicoline reduces apoptosis induced by 100 nM staurosporine for 12 h in SH-SY5Y cells. This effect is higher with pre-treatment of 60 mM citicoline for 24 h after staurosporine challenge. Moreover, citicoline treatment restores glutathione redox ratio diminished after staurosporine challenge. Finally, citicoline also reduces the expression levels of active caspase-3 and specific PARP-cleaved products of 89 kDa resulting from staurosporine exposure when citicoline is added to the culture medium 24 h before staurosporine. These findings demonstrate that citicoline affects the staurosporine-induced apoptosis cell-signalling pathway by interacting with the glutathione system and by inhibiting caspase-3 in SH-SY5Y human neuroblastoma cells.
authors.affiliation: Departament de Biologia Cellular i Anatomia Patològica, Universitat de Barcelona, Campus de Bellvitge, carrer Feixa Llarga sn, 08907, Hospitalet de Llobregat, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Barrachina
authors.forename: Julio
authors.initials: J
authors.lastname: Secades
authors.forename: Rafael
authors.initials: R
authors.lastname: Lozano
authors.forename: Cristina
authors.initials: C
authors.lastname: Gómez-Santos
authors.forename: Santiago
authors.initials: S
authors.lastname: Ambrosio
authors.forename: Isidro
authors.initials: I
authors.lastname: Ferrer
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D003566:Cytidine Diphosphate Choline / Q000378:metabolism / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005978:Glutathione / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D009447:Neuroblastoma; D018697:Nootropic Agents / Q000378:metabolism / Q000494:pharmacology*; D010084:Oxidation-Reduction / Q000187:drug effects; D019311:Staurosporine / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D018697:Nootropic Agents; D003566:Cytidine Diphosphate Choline; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D005978:Glutathione; D019311:Staurosporine