title: Guanosine protects C6 astroglial cells against azide-induced oxidative damage: a putative role of heme oxygenase 1.
abstract: Guanosine, a guanine-based purine, is an extracellular signaling molecule that is released from astrocytes and shows neuroprotective effects in several in vivo and in vitro studies. Our group recently showed that guanosine presents antioxidant properties in C6 astroglial cells. The heme oxygenase 1 signaling pathway is associated with protection against oxidative stress. Azide, an inhibitor of the respiratory chain, is frequently used in experimental models to induce oxidative and nitrosative stress. Thus, the goal of this study was to investigate the effect of guanosine on azide-induced oxidative damage in C6 astroglial cells. Azide treatment of these cells resulted in several detrimental effects, including induction of cytotoxicity and mitochondrial dysfunction, increased levels of reactive oxygen/nitrogen species, inducible nitric oxide synthase expression and NADPH oxidase, decreased glutamate uptake and EAAC1 glutamate transporter expression, decreased glutathione (GSH) levels, and decreased activities of glutamine synthetase (GS), superoxide dismutase and catalase (CAT). The treatment also increased nuclear factor-κB activation and the release of proinflammatory cytokines tumor necrosis factor α and IL-1β. Guanosine strongly prevented these effects, protecting glial cells against azide-induced cytotoxicity and modulating glial, oxidative and inflammatory responses through the activation of the heme oxygenase 1 pathway. These observations reinforce and support the role of guanosine as an antioxidant molecule against oxidative damage. Guanosine protects against azide-induced oxidative damage in C6 astroglial cells. Azide-induced mitochondrial dysfunction (1); increased reactive oxygen species/reactive nitrogen species levels (2); decreased glutamate uptake (3), GS activity (4), GSH levels (5), and SOD (6) and CAT (7) activities; increased glutathione peroxidase (GPx) (8) and NADPH oxidase (9) activities and cellular superoxide levels (10); increased NF-κB activation (11), TNF-α and IL-1β levels (12); and induced iNOS expression (13). Guanosine prevented these effects through the HO1 signaling pathway, thus our findings support the antioxidant effects of guanosine.
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, Porto Alegre, RS, Brazil.
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: 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; D001253:Astrocytes / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D001386:Azides / Q000633:toxicity*; D002460:Cell Line; D002478:Cells, Cultured; D006151:Guanosine / Q000494:pharmacology*; D006419:Heme Oxygenase (Decyclizing) / Q000502:physiology*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001386:Azides; D018696:Neuroprotective Agents; D006151:Guanosine; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat
keywords: C6 astroglial cells; azide; glioprotective molecule; guanosine; heme oxygenase 1