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Guanosine controls inflammatory pathways to afford neuroprotection of hippocampal slices under oxygen and glucose deprivation conditions.
J Neurochem. 2013 Aug; 126(4):437-50.JN

Abstract

Guanosine (GUO) is an endogenous modulator of glutamatergic excitotoxicity and has been shown to promote neuroprotection in in vivo and in vitro models of neurotoxicity. This study was designed to understand the neuroprotective mechanism of GUO against oxidative damage promoted by oxygen/glucose deprivation and reoxygenation (OGD). GUO (100 μM) reduced reactive oxygen species production and prevented mitochondrial membrane depolarization induced by OGD. GUO also exhibited anti-inflammatory actions as inhibition of nuclear factor kappa B activation and reduction of inducible nitric oxide synthase induction induced by OGD. These GUO neuroprotective effects were mediated by adenosine A1 receptor, phosphatidylinositol-3 kinase and MAPK/ERK. Furthermore, GUO recovered the impairment of glutamate uptake caused by OGD, an effect that occurred via a Pertussis toxin-sensitive G-protein-coupled signaling, blockade of adenosine A2A receptors (A2A R), but not via A1 receptor. The modulation of glutamate uptake by GUO also involved MAPK/ERK activation. In conclusion, GUO, by modulating adenosine receptor function and activating MAPK/ERK, affords neuroprotection of hippocampal slices subjected to OGD by a mechanism that implicates the following: (i) prevention of mitochondrial membrane depolarization, (ii) reduction of oxidative stress, (iii) regulation of inflammation by inhibition of nuclear factor kappa B and inducible nitric oxide synthase, and (iv) promoting glutamate uptake.

Authors+Show Affiliations

Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23713463

Citation

Dal-Cim, Tharine, et al. "Guanosine Controls Inflammatory Pathways to Afford Neuroprotection of Hippocampal Slices Under Oxygen and Glucose Deprivation Conditions." Journal of Neurochemistry, vol. 126, no. 4, 2013, pp. 437-50.
Dal-Cim T, Ludka FK, Martins WC, et al. Guanosine controls inflammatory pathways to afford neuroprotection of hippocampal slices under oxygen and glucose deprivation conditions. J Neurochem. 2013;126(4):437-50.
Dal-Cim, T., Ludka, F. K., Martins, W. C., Reginato, C., Parada, E., Egea, J., López, M. G., & Tasca, C. I. (2013). Guanosine controls inflammatory pathways to afford neuroprotection of hippocampal slices under oxygen and glucose deprivation conditions. Journal of Neurochemistry, 126(4), 437-50. https://doi.org/10.1111/jnc.12324
Dal-Cim T, et al. Guanosine Controls Inflammatory Pathways to Afford Neuroprotection of Hippocampal Slices Under Oxygen and Glucose Deprivation Conditions. J Neurochem. 2013;126(4):437-50. PubMed PMID: 23713463.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Guanosine controls inflammatory pathways to afford neuroprotection of hippocampal slices under oxygen and glucose deprivation conditions. AU - Dal-Cim,Tharine, AU - Ludka,Fabiana K, AU - Martins,Wagner C, AU - Reginato,Charlise, AU - Parada,Esther, AU - Egea,Javier, AU - López,Manuela G, AU - Tasca,Carla I, Y1 - 2013/06/17/ PY - 2013/04/29/received PY - 2013/05/02/accepted PY - 2013/5/30/entrez PY - 2013/5/30/pubmed PY - 2013/10/24/medline KW - adenosine receptors KW - glutamate uptake KW - guanosine KW - hippocampal slices KW - mitogen-activated protein kinases signaling KW - oxygen/glucose deprivation and reoxygenation SP - 437 EP - 50 JF - Journal of neurochemistry JO - J Neurochem VL - 126 IS - 4 N2 - Guanosine (GUO) is an endogenous modulator of glutamatergic excitotoxicity and has been shown to promote neuroprotection in in vivo and in vitro models of neurotoxicity. This study was designed to understand the neuroprotective mechanism of GUO against oxidative damage promoted by oxygen/glucose deprivation and reoxygenation (OGD). GUO (100 μM) reduced reactive oxygen species production and prevented mitochondrial membrane depolarization induced by OGD. GUO also exhibited anti-inflammatory actions as inhibition of nuclear factor kappa B activation and reduction of inducible nitric oxide synthase induction induced by OGD. These GUO neuroprotective effects were mediated by adenosine A1 receptor, phosphatidylinositol-3 kinase and MAPK/ERK. Furthermore, GUO recovered the impairment of glutamate uptake caused by OGD, an effect that occurred via a Pertussis toxin-sensitive G-protein-coupled signaling, blockade of adenosine A2A receptors (A2A R), but not via A1 receptor. The modulation of glutamate uptake by GUO also involved MAPK/ERK activation. In conclusion, GUO, by modulating adenosine receptor function and activating MAPK/ERK, affords neuroprotection of hippocampal slices subjected to OGD by a mechanism that implicates the following: (i) prevention of mitochondrial membrane depolarization, (ii) reduction of oxidative stress, (iii) regulation of inflammation by inhibition of nuclear factor kappa B and inducible nitric oxide synthase, and (iv) promoting glutamate uptake. SN - 1471-4159 UR - https://www.unboundmedicine.com/medline/citation/23713463/Guanosine_controls_inflammatory_pathways_to_afford_neuroprotection_of_hippocampal_slices_under_oxygen_and_glucose_deprivation_conditions_ L2 - https://doi.org/10.1111/jnc.12324 DB - PRIME DP - Unbound Medicine ER -