title: Vitis labrusca extract effects on cellular dynamics and redox modulations in a SH-SY5Y neuronal cell model: a similar role to lithium.
abstract: Oxidative stress and calcium imbalance are consistently reported in bipolar disorder (BD). Polymorphism of voltage-dependent calcium channel, L type, alpha 1C subunit (CACNA1c), which is responsible for the regulation of calcium influx, was also shown to have a strong association with BD. These alterations can lead to a number of different consequences in the cell including production of reactive species causing oxidative damage to proteins, lipids and DNA. Lithium is the most frequent medication used for the treatment of BD. Despite lithium's effects, long-term use can result in many negative side effects. Therefore, there is an urgent need for the development of drugs that may have similar biological effects as lithium without the negative consequences. Moreover, polyphenols are secondary metabolites of plants that present multi-faceted molecular abilities, such as regulation of cellular responses. Vitis labrusca extract (VLE), a complex mixture of polyphenols obtained from seeds of winery wastes of V. labrusca, was previously characterized by our group. This extract presented powerful antioxidant and neuroprotective properties. Therefore, the ability of VLE to ameliorate the consequences of hydrogen peroxide (H2O2)-induced redox alterations to cell viability, intracellular calcium levels and the relative levels of the calcium channel CACNA1c in comparison to lithium's effects were evaluated using a neuroblastoma cell model. H2O2 treatment increased cell mortality through apoptotic and necrotic pathways leading to an increase in intracellular calcium levels and alterations to relative CACNA1c levels. VLE and lithium were found to similarly ameliorate cell mortality through regulation of the apoptotic/necrotic pathways, decreasing intracellular calcium levels and preventing alterations to the relative levels of CACNA1c. The findings of this study suggest that VLE exhibits protective properties against oxidative stress-induced alterations similar to that of lithium. These findings suggest that VLE may be an attractive potential candidate as a novel therapeutic agent for BD.
authors.affiliation: Department of Psychiatry, University of Toronto, 250 College Street, Toronto, ON, Canada M5T 1R8; Centre for Addiction and Mental Health, 250 College Street, Toronto, ON, Canada M5T 1R8; Institute of Biotechnology, University of Caxias do Sul, 1130 Getulio Vargas Street, Caxias do Sul, RS 95070 560, Brazil.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Scola
authors.affiliation: Department of Pharmacology, University of Toronto, Medical Science Building, 1 King's College Circle, Toronto, ON Canada M5S 1A8.
authors.forename: Victoria Louise Marina
authors.initials: VL
authors.lastname: Laliberte
authors.affiliation: Department of Pharmacology, University of Toronto, Medical Science Building, 1 King's College Circle, Toronto, ON Canada M5S 1A8.
authors.forename: Helena Kyunghee
authors.initials: HK
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, University of Toronto, Medical Science Building, 1 King's College Circle, Toronto, ON Canada M5S 1A8.
authors.forename: Arsene
authors.initials: A
authors.lastname: Pinguelo
authors.affiliation: Institute of Biotechnology, University of Caxias do Sul, 1130 Getulio Vargas Street, Caxias do Sul, RS 95070 560, Brazil.
authors.forename: Mirian
authors.initials: M
authors.lastname: Salvador
authors.affiliation: Department of Psychiatry, University of Toronto, 250 College Street, Toronto, ON, Canada M5T 1R8; Centre for Addiction and Mental Health, 250 College Street, Toronto, ON, Canada M5T 1R8; Department of Pharmacology, University of Toronto, Medical Science Building, 1 King's College Circle, Toronto, ON Canada M5S 1A8.
authors.forename: L Trevor
authors.initials: LT
authors.lastname: Young
authors.affiliation: Department of Psychiatry, University of Toronto, 250 College Street, Toronto, ON, Canada M5T 1R8; Centre for Addiction and Mental Health, 250 College Street, Toronto, ON, Canada M5T 1R8; Institute of Biotechnology, University of Caxias do Sul, 1130 Getulio Vargas Street, Caxias do Sul, RS 95070 560, Brazil; Department of Pharmacology, University of Toronto, Medical Science Building, 1 King's College Circle, Toronto, ON Canada M5S 1A8. Electronic address: ana.andreazza@utoronto.ca.
authors.forename: Ana Cristina
authors.initials: AC
authors.lastname: Andreazza
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001714:Bipolar Disorder / Q000188:drug therapy; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D006801:Humans; D008094:Lithium / Q000494:pharmacology*; D009336:Necrosis; D009474:Neurons / Q000187:drug effects*; D010084:Oxidation-Reduction; D010936:Plant Extracts / Q000494:pharmacology*; D027843:Vitis / Q000737:chemistry*
chemical_list: C079146:CACNA1C protein, human; D020746:Calcium Channels, L-Type; D010936:Plant Extracts; D008094:Lithium
keywords: CACNA1c; Grape seed extract; Intracellular calcium levels; Lithium; Neuroblastoma cells; Polyphenols