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Atorvastatin prevents cell damage via modulation of oxidative stress, glutamate uptake and glutamine synthetase activity in hippocampal slices subjected to oxygen/glucose deprivation.
Neurochem Int. 2013 Jun; 62(7):948-55.NI

Abstract

Oxygen-glucose deprivation (OGD) in brain cells increases extracellular glutamate concentration leading to excitotoxicity. Glutamate uptake from the synaptic cleft is carried out by glutamate transporters, which are likely to be modulated by oxidative stress. Therefore, oxidative stress is associated with reduced activity of glutamate transporters and glutamine synthetase, thus increasing extracellular glutamate levels that may aggravate damage to brain cells. Atorvastatin, a cholesterol-lowering agent, has been shown to exert neuroprotective effects. The aim of this study was to investigate if in vivo atorvastatin treatment would have protective effects against hippocampal slices subjected to OGD, ex vivo. Atorvastatin pretreatment promoted increased cell viability after OGD and reoxygenation of hippocampal slices. Atorvastatin-induced neuroprotection may be related to diminished oxidative stress, since it prevented OGD-induced decrement of non-proteic thiols (NPSH) levels and increase in the production of reactive oxygen species (ROS). Atorvastatin pretreatment also prevented the OGD-induced decrease in glutamate uptake and glutamine synthetase activity, although it had no effect on OGD-induced excitatory aminoacids release. Addition of cholesterol before OGD and reoxygenation, abolished the protective effect of atorvastatin on cellular viability as well as on glutamate uptake and glutamine synthetase activity. Therefore, atorvastatin is capable of preventing OGD-induced cell death, an effect achieved due to modulation of glutamate uptake and glutamine synthetase activity, and associated with diminished oxidative stress. Additionally, atorvastatin effects were dependent on its action on cholesterol synthesis inhibition. Thus, atorvastatin might be a useful strategy in the prevention of glutamate exitotoxicity involved in brain injuries such as vascular disorders.

Authors+Show Affiliations

Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade, 88040-900 Florianópolis, SC, Brazil.No 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

23500607

Citation

Vandresen-Filho, Samuel, et al. "Atorvastatin Prevents Cell Damage Via Modulation of Oxidative Stress, Glutamate Uptake and Glutamine Synthetase Activity in Hippocampal Slices Subjected to Oxygen/glucose Deprivation." Neurochemistry International, vol. 62, no. 7, 2013, pp. 948-55.
Vandresen-Filho S, Martins WC, Bertoldo DB, et al. Atorvastatin prevents cell damage via modulation of oxidative stress, glutamate uptake and glutamine synthetase activity in hippocampal slices subjected to oxygen/glucose deprivation. Neurochem Int. 2013;62(7):948-55.
Vandresen-Filho, S., Martins, W. C., Bertoldo, D. B., Mancini, G., Herculano, B. A., de Bem, A. F., & Tasca, C. I. (2013). Atorvastatin prevents cell damage via modulation of oxidative stress, glutamate uptake and glutamine synthetase activity in hippocampal slices subjected to oxygen/glucose deprivation. Neurochemistry International, 62(7), 948-55. https://doi.org/10.1016/j.neuint.2013.03.002
Vandresen-Filho S, et al. Atorvastatin Prevents Cell Damage Via Modulation of Oxidative Stress, Glutamate Uptake and Glutamine Synthetase Activity in Hippocampal Slices Subjected to Oxygen/glucose Deprivation. Neurochem Int. 2013;62(7):948-55. PubMed PMID: 23500607.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Atorvastatin prevents cell damage via modulation of oxidative stress, glutamate uptake and glutamine synthetase activity in hippocampal slices subjected to oxygen/glucose deprivation. AU - Vandresen-Filho,Samuel, AU - Martins,Wagner C, AU - Bertoldo,Daniela B, AU - Mancini,Gianni, AU - Herculano,Bruno A, AU - de Bem,Andreza F, AU - Tasca,Carla I, Y1 - 2013/03/14/ PY - 2012/07/11/received PY - 2013/02/28/revised PY - 2013/03/03/accepted PY - 2013/3/19/entrez PY - 2013/3/19/pubmed PY - 2013/11/16/medline SP - 948 EP - 55 JF - Neurochemistry international JO - Neurochem Int VL - 62 IS - 7 N2 - Oxygen-glucose deprivation (OGD) in brain cells increases extracellular glutamate concentration leading to excitotoxicity. Glutamate uptake from the synaptic cleft is carried out by glutamate transporters, which are likely to be modulated by oxidative stress. Therefore, oxidative stress is associated with reduced activity of glutamate transporters and glutamine synthetase, thus increasing extracellular glutamate levels that may aggravate damage to brain cells. Atorvastatin, a cholesterol-lowering agent, has been shown to exert neuroprotective effects. The aim of this study was to investigate if in vivo atorvastatin treatment would have protective effects against hippocampal slices subjected to OGD, ex vivo. Atorvastatin pretreatment promoted increased cell viability after OGD and reoxygenation of hippocampal slices. Atorvastatin-induced neuroprotection may be related to diminished oxidative stress, since it prevented OGD-induced decrement of non-proteic thiols (NPSH) levels and increase in the production of reactive oxygen species (ROS). Atorvastatin pretreatment also prevented the OGD-induced decrease in glutamate uptake and glutamine synthetase activity, although it had no effect on OGD-induced excitatory aminoacids release. Addition of cholesterol before OGD and reoxygenation, abolished the protective effect of atorvastatin on cellular viability as well as on glutamate uptake and glutamine synthetase activity. Therefore, atorvastatin is capable of preventing OGD-induced cell death, an effect achieved due to modulation of glutamate uptake and glutamine synthetase activity, and associated with diminished oxidative stress. Additionally, atorvastatin effects were dependent on its action on cholesterol synthesis inhibition. Thus, atorvastatin might be a useful strategy in the prevention of glutamate exitotoxicity involved in brain injuries such as vascular disorders. SN - 1872-9754 UR - https://www.unboundmedicine.com/medline/citation/23500607/Atorvastatin_prevents_cell_damage_via_modulation_of_oxidative_stress_glutamate_uptake_and_glutamine_synthetase_activity_in_hippocampal_slices_subjected_to_oxygen/glucose_deprivation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0197-0186(13)00074-0 DB - PRIME DP - Unbound Medicine ER -