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.

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.

Perspectiva monggráfica del cáncer pulmonar: un enfoque molecular y la metástasis al cerebro

El cáncer es una de las principales causas de muerte en el mundo. En México, al igual que en los países desarrollados, el cáncer pulmonar es uno de los más frecuentes y, de forma importante, la evolución y pronóstico de la enfermedad es bastante más grave cuando se torna metastásico. Metástasis: Las siembras celulares a distancia constituyen la complicación más grave del cáncer. Cuando las metástasis se dirigen al sistema nervioso central, las probabilidades de sobrevida o recuperación disminuyen. Generalmente, la principal causa de muerte del cáncer son las metástasis. El fenómeno de migración celular y metástasis definitivamente no es azaroso. Existe evidencia clara de que hay predisposición celular tumoral para que suceda; además, se ha demostrado que la célula que migra lo hace a través de la participación de diversas moléculas de adhesión, proteínas que reconocen carbohidratos y fenómenos citocinéticos relacionados. Glicosilación: El papel que desempeñan los oligosacáridos de superficie celular en el reconocimiento, señalización, migración, interacción célula-célula y célula-matriz extracelular es crucial para que las células cancerosas se desarrollen, proliferen, migren, invadan y metastatizen. Las modificaciones en la expresión de los oligosacáridos de superficie celular influyen en la carcinogénesis y metástasis. Conclusión: En esta revisión se exponen las evidencias que marcan las bases moleculares de la carcinogénesis pulmonar, por ser tan frecuente en nuestro medio, y los fenómenos de migración celular que involucran la metástasis al cerebro, siendo ésta la más grave de las complicaciones del cáncer.

Cancer is one of the main causes of death in the world. In Mexico, like in developed countries, lung cancer is very frequent and particularly severe when there is metastatic disease. Metastasis: Cell sowing at a distance is the worst complication of cancer. The main cause of death in cancer is metastasis. Cell migration and metastasis are not randomized. There is evidence of cellular tumor predisposition for metastasis; furthermore, the migrating cell does it through the participation of several adhesion molecules, carbohydrate-ligand proteins and related cytokinetics phenomena. When metastatic cells are deposited in the central nervous system, the probabilities for recuperation or survival are nil. Glycosylation: The role of cell-surface oligosaccharides in the recognition, signalization, migration, cell-cell and cell-extracellular matrix interactions, is crucial for the development, proliferation, migration, invasion and eventual metastasis of the neoplastic cell. Modifications in the expression of the cell-surface oligosaccharides have influence in carcinogenesis and metastasis. Conclusions: In this review, we present the evidence supporting the molecular basis of lung carcinogenesis, and the cell migration phenomena which are involved in brain metastasis.