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Guanosine enhances glutamate uptake and oxidation, preventing oxidative stress in mouse hippocampal slices submitted to high glutamate levels.
Nonose, Y; Pieper, L Z; da Silva, J S; Longoni, A; Apel, R V; Meira-Martins, L A; Grings, M; Leipnitz, G; Souza, D O; de Assis, A M.
Affiliation
  • Nonose Y; Graduate Program in Biological Sciences: Biochemistry, ICBS, Universidade Federal do Rio Grande do Sul - UFRGS, Porto Alegre, RS 90035-003, Brazil.
  • Pieper LZ; Graduate Program in Health and Behavior, Center of Health Science, Universidade Católica de Pelotas - UCPel, Pelotas, RS 96015-560, Brazil.
  • da Silva JS; Graduate Program in Biological Sciences: Biochemistry, ICBS, Universidade Federal do Rio Grande do Sul - UFRGS, Porto Alegre, RS 90035-003, Brazil.
  • Longoni A; Graduate Program in Biological Sciences: Biochemistry, ICBS, Universidade Federal do Rio Grande do Sul - UFRGS, Porto Alegre, RS 90035-003, Brazil; Graduate Program in Health and Behavior, Center of Health Science, Universidade Católica de Pelotas - UCPel, Pelotas, RS 96015-560, Brazil.
  • Apel RV; Graduate Program in Biological Sciences: Biochemistry, ICBS, Universidade Federal do Rio Grande do Sul - UFRGS, Porto Alegre, RS 90035-003, Brazil.
  • Meira-Martins LA; Graduate Program in Biological Sciences: Biochemistry, ICBS, Universidade Federal do Rio Grande do Sul - UFRGS, Porto Alegre, RS 90035-003, Brazil.
  • Grings M; Graduate Program in Biological Sciences: Biochemistry, ICBS, Universidade Federal do Rio Grande do Sul - UFRGS, Porto Alegre, RS 90035-003, Brazil.
  • Leipnitz G; Graduate Program in Biological Sciences: Biochemistry, ICBS, Universidade Federal do Rio Grande do Sul - UFRGS, Porto Alegre, RS 90035-003, Brazil; Department of Biochemistry, Universidade Federal do Rio Grande do Sul - UFRGS, Porto Alegre, RS 90035-003, Brazil.
  • Souza DO; Graduate Program in Biological Sciences: Biochemistry, ICBS, Universidade Federal do Rio Grande do Sul - UFRGS, Porto Alegre, RS 90035-003, Brazil; Department of Biochemistry, Universidade Federal do Rio Grande do Sul - UFRGS, Porto Alegre, RS 90035-003, Brazil. Electronic address: diogo@ufrgs.br.
  • de Assis AM; Graduate Program in Biological Sciences: Biochemistry, ICBS, Universidade Federal do Rio Grande do Sul - UFRGS, Porto Alegre, RS 90035-003, Brazil; Graduate Program in Health and Behavior, Center of Health Science, Universidade Católica de Pelotas - UCPel, Pelotas, RS 96015-560, Brazil.
Brain Res ; 1748: 147080, 2020 12 01.
Article in En | MEDLINE | ID: mdl-32866546
Glutamate (Glu) is the main mammalian brain neurotransmitter. Concerning the glutamatergic neurotransmission, excessive levels of glutamate in the synaptic cleft are extremally harmful. This phenomenon, named as excitotoxicity is involved in various acute and chronic brain diseases. Guanosine (GUO), an endogenous guanine nucleoside, possesses neuroprotective effects in several experimental models of glutamatergic excitotoxicity, an effect accompanied by an increase in astrocytic glutamate uptake. Therefore, the objective of this study was to investigate the involvement of an additional putative parameter, glutamate oxidation to CO2, involved in ex-vivo GUO neuroprotective effects in mouse hippocampal slices submitted to glutamatergic excitotoxicity. Mice were sacrificed by decapitation, the hippocampi were removed and sliced. The slices were incubated for various times and concentrations of Glu and GUO. First, the concentration of Glu that produced an increase in L-[14C(U)]-Glu oxidation to CO2 without cell injury was determined at different time points (between 0 and 90 min); 1000 µM Glu increased Glu oxidation between 30 and 60 min of incubation without cell injury. Under these conditions (Glu concentration and incubation time), 100 µM GUO increased Glu oxidation (35%). Additionally, 100 µM GUO increased L-[3,4-3H]-glutamate uptake (45%) in slices incubated with 1000 µM Glu (0-30 min). Furthermore, 1000  µM Glu increased reactive species levels, SOD activity, and decreased GPx activity, and GSH content after 30 and 60 min; 100 µM GUO prevented these effects. This is the first study demonstrating that GUO simultaneously promoted an increase in the uptake and utilization of Glu in excitotoxicity-like conditions preventing redox imbalance.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Oxidative Stress / Neuroprotective Agents / Glutamic Acid / Guanosine / Hippocampus / Antioxidants Limits: Animals Language: En Journal: Brain Res Year: 2020 Document type: Article Affiliation country: Brazil Country of publication: Netherlands

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Oxidative Stress / Neuroprotective Agents / Glutamic Acid / Guanosine / Hippocampus / Antioxidants Limits: Animals Language: En Journal: Brain Res Year: 2020 Document type: Article Affiliation country: Brazil Country of publication: Netherlands