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Selenium reduces the proapoptotic signaling associated to NF-kappaB pathway and stimulates glutathione peroxidase activity during excitotoxic damage produced by quinolinate in rat corpus striatum.
Synapse. 2005 Dec 15; 58(4):258-66.S

Abstract

Quinolinate (QUIN) neurotoxicity has been attributed to degenerative events in nerve tissue produced by sustained activation of N-methyl-D-aspartate receptor (NMDAr) and oxidative stress. We have recently described the protective effects that selenium (Se), an antioxidant, produces on different markers of QUIN-induced neurotoxicity (Santamaría et al., 2003, J Neurochem 86:479-488.). However, the mechanisms by which Se exerts its protective actions remain unclear. Since some of these events are thought to be related with inhibition of deadly molecular cascades through the activation of antioxidant selenoproteins, in this study we investigated the effects of Se on QUIN-induced cell damage elicited by the nuclear factor kappaB (NF-kappaB) pathway, as well as the time-course response of striatal glutathione peroxidase (GPx) activity. Se (sodium selenite, 0.625 mg/kg/day, i.p.) was administered to rats for 5 days, and 120 min after the last administration, animals received a single striatal injection of QUIN (240 nmol/mul). Twenty-four hours later, their striata were tested for the expression of IkappaB-alpha (the NF-kappaB cytosolic binding protein), the immunohistochemical expression of NF-kappaB (evidenced as nuclear expression of P65), caspase-3-like activation, and DNA fragmentation. Additional groups were killed at 2, 6, and 24 h for measurement of GPx activity. Se reduced the QUIN-induced decrease in IkappaB-alpha expression, evidencing a reduction in its cytosolic degradation. Se also prevented the QUIN-induced increase in P65-immunoreactive cells, suggesting a reduction of NF-kappaB nuclear translocation. Caspase-3-like activation and DNA fragmentation produced by QUIN were also inhibited by Se. Striatal GPx activity was stimulated by Se at 2 and 6 h, but not at 24 h postlesion. Altogether, these data suggest that the protective effects exerted by Se on QUIN-induced neurotoxicity are partially mediated by the inhibition of proapoptotic events underlying IkappaB-alpha degradation, NF-kappaB nuclear translocation, and caspase-3-like activation in the rat striatum, probably involving the early activation of GPx.

Authors+Show Affiliations

Laboratorio de Aminoácidos Excitadores, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, SSA. México DF.No affiliation info availableNo 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

Language

eng

PubMed ID

16206188

Citation

Santamaría, Abel, et al. "Selenium Reduces the Proapoptotic Signaling Associated to NF-kappaB Pathway and Stimulates Glutathione Peroxidase Activity During Excitotoxic Damage Produced By Quinolinate in Rat Corpus Striatum." Synapse (New York, N.Y.), vol. 58, no. 4, 2005, pp. 258-66.
Santamaría A, Vázquez-Román B, La Cruz VP, et al. Selenium reduces the proapoptotic signaling associated to NF-kappaB pathway and stimulates glutathione peroxidase activity during excitotoxic damage produced by quinolinate in rat corpus striatum. Synapse. 2005;58(4):258-66.
Santamaría, A., Vázquez-Román, B., La Cruz, V. P., González-Cortés, C., Trejo-Solís, M. C., Galván-Arzate, S., Jara-Prado, A., Guevara-Fonseca, J., & Ali, S. F. (2005). Selenium reduces the proapoptotic signaling associated to NF-kappaB pathway and stimulates glutathione peroxidase activity during excitotoxic damage produced by quinolinate in rat corpus striatum. Synapse (New York, N.Y.), 58(4), 258-66.
Santamaría A, et al. Selenium Reduces the Proapoptotic Signaling Associated to NF-kappaB Pathway and Stimulates Glutathione Peroxidase Activity During Excitotoxic Damage Produced By Quinolinate in Rat Corpus Striatum. Synapse. 2005 Dec 15;58(4):258-66. PubMed PMID: 16206188.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Selenium reduces the proapoptotic signaling associated to NF-kappaB pathway and stimulates glutathione peroxidase activity during excitotoxic damage produced by quinolinate in rat corpus striatum. AU - Santamaría,Abel, AU - Vázquez-Román,Beatriz, AU - La Cruz,Verónica Pérez-De, AU - González-Cortés,Carolina, AU - Trejo-Solís,Ma Cristina, AU - Galván-Arzate,Sonia, AU - Jara-Prado,Aurelio, AU - Guevara-Fonseca,Jorge, AU - Ali,Syed F, PY - 2005/10/6/pubmed PY - 2006/1/19/medline PY - 2005/10/6/entrez SP - 258 EP - 66 JF - Synapse (New York, N.Y.) JO - Synapse VL - 58 IS - 4 N2 - Quinolinate (QUIN) neurotoxicity has been attributed to degenerative events in nerve tissue produced by sustained activation of N-methyl-D-aspartate receptor (NMDAr) and oxidative stress. We have recently described the protective effects that selenium (Se), an antioxidant, produces on different markers of QUIN-induced neurotoxicity (Santamaría et al., 2003, J Neurochem 86:479-488.). However, the mechanisms by which Se exerts its protective actions remain unclear. Since some of these events are thought to be related with inhibition of deadly molecular cascades through the activation of antioxidant selenoproteins, in this study we investigated the effects of Se on QUIN-induced cell damage elicited by the nuclear factor kappaB (NF-kappaB) pathway, as well as the time-course response of striatal glutathione peroxidase (GPx) activity. Se (sodium selenite, 0.625 mg/kg/day, i.p.) was administered to rats for 5 days, and 120 min after the last administration, animals received a single striatal injection of QUIN (240 nmol/mul). Twenty-four hours later, their striata were tested for the expression of IkappaB-alpha (the NF-kappaB cytosolic binding protein), the immunohistochemical expression of NF-kappaB (evidenced as nuclear expression of P65), caspase-3-like activation, and DNA fragmentation. Additional groups were killed at 2, 6, and 24 h for measurement of GPx activity. Se reduced the QUIN-induced decrease in IkappaB-alpha expression, evidencing a reduction in its cytosolic degradation. Se also prevented the QUIN-induced increase in P65-immunoreactive cells, suggesting a reduction of NF-kappaB nuclear translocation. Caspase-3-like activation and DNA fragmentation produced by QUIN were also inhibited by Se. Striatal GPx activity was stimulated by Se at 2 and 6 h, but not at 24 h postlesion. Altogether, these data suggest that the protective effects exerted by Se on QUIN-induced neurotoxicity are partially mediated by the inhibition of proapoptotic events underlying IkappaB-alpha degradation, NF-kappaB nuclear translocation, and caspase-3-like activation in the rat striatum, probably involving the early activation of GPx. SN - 0887-4476 UR - https://www.unboundmedicine.com/medline/citation/16206188/Selenium_reduces_the_proapoptotic_signaling_associated_to_NF_kappaB_pathway_and_stimulates_glutathione_peroxidase_activity_during_excitotoxic_damage_produced_by_quinolinate_in_rat_corpus_striatum_ L2 - https://doi.org/10.1002/syn.20206 DB - PRIME DP - Unbound Medicine ER -