Tags

Type your tag names separated by a space and hit enter

Guanosine Neuroprotective Action in Hippocampal Slices Subjected to Oxygen and Glucose Deprivation Restores ATP Levels, Lactate Release and Glutamate Uptake Impairment: Involvement of Nitric Oxide.
Neurochem Res. 2020 Sep; 45(9):2217-2229.NR

Abstract

Stroke is a major cause of disability and death worldwide. Oxygen and glucose deprivation (OGD) in brain tissue preparations can reproduce several pathological features induced by stroke providing a valuable ex vivo protocol for studying the mechanism of action of neuroprotective agents. Guanosine, an endogenous guanine nucleoside, promotes neuroprotection in vivo and in vitro models of neurotoxicity. We previously showed that guanosine protective effect was mimicked by inhibition of nitric oxide synthases (NOS) activity. This study was designed to investigate the involvement of nitric oxide (NO) in the mechanisms related to the protective role of guanosine in rat hippocampal slices subjected to OGD followed by reoxygenation (OGD/R). Guanosine (100 μM) and the pan-NOS inhibitor, L-NAME (1 mM) afforded protection to hippocampal slices subjected to OGD/R. The presence of NO donors, DETA-NO (800 μM) or SNP (5 μM) increased reactive species production, and abolished the protective effect of guanosine or L-NAME against OGD/R. Guanosine or L-NAME treatment prevented the impaired ATP production, lactate release, and glutamate uptake following OGD/R. The presence of a NO donor also abolished the beneficial effects of guanosine or L-NAME on bioenergetics and glutamate uptake. These results showed, for the first time, that guanosine may regulate cellular bioenergetics in hippocampal slices subjected to OGD/R injury by a mechanism that involves the modulation of NO levels.

Authors+Show Affiliations

Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade, Florianópolis, SC, 88040-900, Brazil. Programa de Pós-Graduação em Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade, Florianópolis, SC, 88040-900, Brazil.Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade, Florianópolis, SC, 88040-900, Brazil. Programa de Pós-Graduação em Neurociências, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade, Florianópolis, SC, 88040-900, Brazil. Programa de Pós-Graduação em Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade, Florianópolis, SC, 88040-900, Brazil.Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade, Florianópolis, SC, 88040-900, Brazil. Programa de Pós-Graduação em Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade, Florianópolis, SC, 88040-900, Brazil. carla.tasca@ufsc.br. Programa de Pós-Graduação em Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil. carla.tasca@ufsc.br. Programa de Pós-Graduação em Neurociências, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil. carla.tasca@ufsc.br.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32666283

Citation

Thomaz, Daniel Tonial, et al. "Guanosine Neuroprotective Action in Hippocampal Slices Subjected to Oxygen and Glucose Deprivation Restores ATP Levels, Lactate Release and Glutamate Uptake Impairment: Involvement of Nitric Oxide." Neurochemical Research, vol. 45, no. 9, 2020, pp. 2217-2229.
Thomaz DT, Andreguetti RR, Binder LB, et al. Guanosine Neuroprotective Action in Hippocampal Slices Subjected to Oxygen and Glucose Deprivation Restores ATP Levels, Lactate Release and Glutamate Uptake Impairment: Involvement of Nitric Oxide. Neurochem Res. 2020;45(9):2217-2229.
Thomaz, D. T., Andreguetti, R. R., Binder, L. B., Scheffer, D. D. L., Corrêa, A. W., Silva, F. R. M. B., & Tasca, C. I. (2020). Guanosine Neuroprotective Action in Hippocampal Slices Subjected to Oxygen and Glucose Deprivation Restores ATP Levels, Lactate Release and Glutamate Uptake Impairment: Involvement of Nitric Oxide. Neurochemical Research, 45(9), 2217-2229. https://doi.org/10.1007/s11064-020-03083-2
Thomaz DT, et al. Guanosine Neuroprotective Action in Hippocampal Slices Subjected to Oxygen and Glucose Deprivation Restores ATP Levels, Lactate Release and Glutamate Uptake Impairment: Involvement of Nitric Oxide. Neurochem Res. 2020;45(9):2217-2229. PubMed PMID: 32666283.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Guanosine Neuroprotective Action in Hippocampal Slices Subjected to Oxygen and Glucose Deprivation Restores ATP Levels, Lactate Release and Glutamate Uptake Impairment: Involvement of Nitric Oxide. AU - Thomaz,Daniel Tonial, AU - Andreguetti,Rafaela Rafognatto, AU - Binder,Luisa Bandeira, AU - Scheffer,Débora da Luz, AU - Corrêa,Alisson Willms, AU - Silva,Fátima Regina Mena Barreto, AU - Tasca,Carla Inês, Y1 - 2020/07/14/ PY - 2020/01/27/received PY - 2020/07/02/accepted PY - 2020/06/23/revised PY - 2020/7/16/pubmed PY - 2021/6/9/medline PY - 2020/7/16/entrez KW - Guanosine KW - Hippocampal slices KW - L-NAME KW - Lactate KW - Nitric oxide KW - Oxygen and glucose deprivation SP - 2217 EP - 2229 JF - Neurochemical research JO - Neurochem Res VL - 45 IS - 9 N2 - Stroke is a major cause of disability and death worldwide. Oxygen and glucose deprivation (OGD) in brain tissue preparations can reproduce several pathological features induced by stroke providing a valuable ex vivo protocol for studying the mechanism of action of neuroprotective agents. Guanosine, an endogenous guanine nucleoside, promotes neuroprotection in vivo and in vitro models of neurotoxicity. We previously showed that guanosine protective effect was mimicked by inhibition of nitric oxide synthases (NOS) activity. This study was designed to investigate the involvement of nitric oxide (NO) in the mechanisms related to the protective role of guanosine in rat hippocampal slices subjected to OGD followed by reoxygenation (OGD/R). Guanosine (100 μM) and the pan-NOS inhibitor, L-NAME (1 mM) afforded protection to hippocampal slices subjected to OGD/R. The presence of NO donors, DETA-NO (800 μM) or SNP (5 μM) increased reactive species production, and abolished the protective effect of guanosine or L-NAME against OGD/R. Guanosine or L-NAME treatment prevented the impaired ATP production, lactate release, and glutamate uptake following OGD/R. The presence of a NO donor also abolished the beneficial effects of guanosine or L-NAME on bioenergetics and glutamate uptake. These results showed, for the first time, that guanosine may regulate cellular bioenergetics in hippocampal slices subjected to OGD/R injury by a mechanism that involves the modulation of NO levels. SN - 1573-6903 UR - https://www.unboundmedicine.com/medline/citation/32666283/Guanosine_Neuroprotective_Action_in_Hippocampal_Slices_Subjected_to_Oxygen_and_Glucose_Deprivation_Restores_ATP_Levels_Lactate_Release_and_Glutamate_Uptake_Impairment:_Involvement_of_Nitric_Oxide_ L2 - https://doi.org/10.1007/s11064-020-03083-2 DB - PRIME DP - Unbound Medicine ER -