title: Changes in the NMR Metabolic Profile of Live Human Neuron-Like SH-SY5Y Cells Exposed to Interferon-α2.
abstract: Interferon (IFN)-α2 is an extensively therapeutically used pro-inflammatory cytokine. Though its efficacy in controlling viral replication and tumor cells proliferation, administration of IFN-α2 is often associated with the development of central side effects. Magnetic resonance spectroscopy studies have demonstrated that IFN-α2 administration affects brain metabolism, however the exact nature of this effect is not completely known. We hypothesized that IFN-α2 can affect metabolic activity of human neuron-like SH-SY5Y cells which possess many characteristics of neurons and represent one of the most used models for studying mechanisms involved in neurotoxicity or neuroprotection. To test our hypothesis we have characterized the metabolic signature of live SH-SY5Y, and their conditioned media, after 24 and 72 h of exposure to vehicle or IFN-α2 (100 ng/ml) by using High Resolution-Magic Angle Spinning (HR-MAS) Nuclear Magnetic Resonance (NMR) spectroscopy. Our results revealed that 1) the use of HR-MAS NMR is ideally suitable for the characterization of the metabolic profile of live cells and their conditioned media without extraction procedures; and 2) a 72 h exposure to IFN-α2 increases the level of metabolites involved in maintaining energetic (including creatine and lactate) and osmotic (such as myo-inositol, scyllo-inositol, taurine and glycerophosphorylcholine) balances in neuron-like cells and of metabolic waste products (namely lactate, ethanol and acetate), glycine and glutamine in their growth media. These results may contribute to gain more knowledge about the IFN-α2 induced effect on the brain and support the interpretation of magnetic resonance spectroscopy studies performed in humans.
authors.affiliation: Department for Life Quality Studies, University of Bologna, Rimini, Italy.
authors.forename: Righi
authors.initials: R
authors.lastname: Valeria
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, via G. Campi, 287, 41125, Modena, Italy.
authors.forename: Schenetti
authors.initials: S
authors.lastname: Luisa
authors.affiliation: Department of Chemical and Geological Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Mucci
authors.initials: M
authors.lastname: Adele
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, via G. Campi, 287, 41125, Modena, Italy.
authors.forename: Benatti
authors.initials: B
authors.lastname: Stefania
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, via G. Campi, 287, 41125, Modena, Italy.
authors.forename: Tascedda
authors.initials: T
authors.lastname: Fabio
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, via G. Campi, 287, 41125, Modena, Italy.
authors.forename: Brunello
authors.initials: B
authors.lastname: Nicoletta
authors.affiliation: Stress, Psychiatry and Immunology Department of Psychological Medicine Institute of Psychiatry, Kings College London, London, UK.
authors.forename: Pariante M
authors.initials: PM
authors.lastname: Carmine
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, via G. Campi, 287, 41125, Modena, Italy. silvia.alboni@unimore.it.
authors.forename: Alboni
authors.initials: A
authors.lastname: Silvia
mesh_terms: D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D017077:Culture Media, Conditioned; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D055442:Metabolome; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D017077:Culture Media, Conditioned; D016898:Interferon-alpha
keywords: HR-MAS NMR; IFN-α; Metabolomics; Neurotoxicity; Osmolytes; SH-SY5Y cells