title: Gliopreventive effects of guanosine against glucose deprivation in vitro.
abstract: Guanosine, a guanine-based purine, is recognized as an extracellular signaling molecule that is released from astrocytes and confers neuroprotective effects in several in vivo and in vitro studies. Astrocytes regulate glucose metabolism, glutamate transport, and defense mechanism against oxidative stress. C6 astroglial cells are widely used as an astrocyte-like cell line to study the astrocytic function and signaling pathways. Our previous studies showed that guanosine modulates the glutamate uptake activity, thus avoiding glutamatergic excitotoxicity and protecting neural cells. The goal of this study was to determine the gliopreventive effects of guanosine against glucose deprivation in vitro in cultured C6 cells. Glucose deprivation induced cytotoxicity, an increase in reactive oxygen and nitrogen species (ROS/RNS) levels and lipid peroxidation as well as affected the metabolism of glutamate, which may impair important astrocytic functions. Guanosine prevented glucose deprivation-induced toxicity in C6 cells by modulating oxidative and nitrosative stress and glial responses, such as the glutamate uptake, the glutamine synthetase activity, and the glutathione levels. Glucose deprivation decreased the level of EAAC1, the main glutamate transporter present in C6 cells. Guanosine also prevented this effect, most likely through PKC, PI3K, p38 MAPK, and ERK signaling pathways. Taken together, these results show that guanosine may represent an important mechanism for protection of glial cells against glucose deprivation. Additionally, this study contributes to a more thorough understanding of the glial- and redox-related protective properties of guanosine in astroglial cells.
authors.affiliation: Departamento de Bioquímica, Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600, Anexo Bairro Santa Cecília, 90035 003, Porto Alegre, Rio Grande do Sul, Brazil, andrequincozes@yahoo.com.br.
authors.forename: André
authors.initials: A
authors.lastname: Quincozes-Santos
authors.forename: Larissa Daniele
authors.initials: LD
authors.lastname: Bobermin
authors.forename: Débora Guerini
authors.initials: DG
authors.lastname: de Souza
authors.forename: Bruna
authors.initials: B
authors.lastname: Bellaver
authors.forename: Carlos-Alberto
authors.initials: CA
authors.lastname: Gonçalves
authors.forename: Diogo Onofre
authors.initials: DO
authors.lastname: Souza
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001253:Astrocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D002460:Cell Line; D005947:Glucose / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D006151:Guanosine / Q000494:pharmacology*; D018696:Neuroprotective Agents; D051381:Rats; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D018696:Neuroprotective Agents; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D006151:Guanosine; D018698:Glutamic Acid; D005947:Glucose