PMID- 16206188
OWN - NLM
STAT- MEDLINE
DCOM- 20060118
LR  - 20131121
IS  - 0887-4476 (Print)
IS  - 0887-4476 (Linking)
VI  - 58
IP  - 4
DP  - 2005 Dec 15
TI  - 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.
PG  - 258-66
AB  - 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 (Santamaria 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.
FAU - Santamaria, Abel
AU  - Santamaria A
AD  - Laboratorio de Aminoacidos Excitadores, Instituto Nacional de Neurologia y 
      Neurocirugia Manuel Velasco Suarez, SSA. Mexico DF.
FAU - Vazquez-Roman, Beatriz
AU  - Vazquez-Roman B
FAU - La Cruz, Veronica Perez-De
AU  - La Cruz VP
FAU - Gonzalez-Cortes, Carolina
AU  - Gonzalez-Cortes C
FAU - Trejo-Solis, Ma Cristina
AU  - Trejo-Solis MC
FAU - Galvan-Arzate, Sonia
AU  - Galvan-Arzate S
FAU - Jara-Prado, Aurelio
AU  - Jara-Prado A
FAU - Guevara-Fonseca, Jorge
AU  - Guevara-Fonseca J
FAU - Ali, Syed F
AU  - Ali SF
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Synapse
JT  - Synapse (New York, N.Y.)
JID - 8806914
RN  - 0 (I kappa B beta protein)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (Neuroprotective Agents)
RN  - EC 1.11.1.9 (Glutathione Peroxidase)
RN  - F6F0HK1URN (Quinolinic Acid)
RN  - H6241UJ22B (Selenium)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Corpus Striatum/*drug effects/metabolism/pathology
MH  - DNA Fragmentation/*drug effects
MH  - Glutathione Peroxidase/drug effects/metabolism
MH  - I-kappa B Proteins/drug effects/metabolism
MH  - Immunohistochemistry
MH  - Male
MH  - NF-kappa B/drug effects/metabolism
MH  - Neuroprotective Agents/*pharmacology
MH  - Quinolinic Acid/*toxicity
MH  - Rats
MH  - Rats, Wistar
MH  - Selenium/*pharmacology
MH  - Signal Transduction/*drug effects
EDAT- 2005/10/06 09:00
MHDA- 2006/01/19 09:00
CRDT- 2005/10/06 09:00
PHST- 2005/10/06 09:00 [pubmed]
PHST- 2006/01/19 09:00 [medline]
PHST- 2005/10/06 09:00 [entrez]
AID - 10.1002/syn.20206 [doi]
PST - ppublish
SO  - Synapse. 2005 Dec 15;58(4):258-66. doi: 10.1002/syn.20206.