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Selenium reduces the proapoptotic signaling associated to NF‐κB pathway and stimulates glutathione peroxidase activity during excitotoxic damage produced by quinolinate in rat corpus striatum
Author(s) -
Santamaría Abel,
VázquezRomán Beatriz,
La cruz Verónica PérezDe,
GonzálezCortés Carolina,
TrejoSolís Ma. Cristina,
GalvánArzate Sonia,
JaraPrado Aurelio,
GuevaraFonseca Jorge,
Ali Syed F.
Publication year - 2005
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.20206
Subject(s) - neurotoxicity , glutathione peroxidase , quinolinate , chemistry , oxidative stress , glutathione , pharmacology , neurotoxin , biochemistry , striatum , dizocilpine , glutamate receptor , medicine , endocrinology , receptor , quinolinic acid , superoxide dismutase , biology , toxicity , dopamine , enzyme , tryptophan , organic chemistry , amino acid
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 κB (NF‐κB) 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/μl). Twenty‐four hours later, their striata were tested for the expression of IκB‐α (the NF‐κB cytosolic binding protein), the immunohistochemical expression of NF‐κB (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 IκB‐α expression, evidencing a reduction in its cytosolic degradation. Se also prevented the QUIN‐induced increase in P65‐immunoreactive cells, suggesting a reduction of NF‐κB 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 IκB‐α degradation, NF‐κB nuclear translocation, and caspase‐3‐like activation in the rat striatum, probably involving the early activation of GPx. Synapse 58:258–266, 2005. Published 2005 Wiley‐Liss, Inc.