S100B effects on primary cortical neurons are determined by RAGE expression and basal NFKB activity: Implications for neuronal-glial cross-talk after ischemia

ALEJANDRO VILLARREAL; ROLANDO X. AVILÉS-REYES; MARIA FLORENCIA ANGELO; PABLO POWER; GABRIEL GUTKIND; ANALIA G. REINES; ALBERTO JAVIER RAMOS

Journal of Neurochemistry

Año: 2009 p. 130 - 150

Neuro-glial cross talk after brain ischemia has been recently recognized as a main determinant of neuronal survival. S100B is a soluble glial-derived protein secreted by reactive astrocytes that was previously shown to have pro-survival or pro-apoptotic effects on neuroblastoma cell lines and hippocampal primary neurons. The receptor for advanced end glycated products (RAGE) seems to be the S100B receptor in the CNS; however RAGE is not expressed in the adult brain. In this report we demonstrated that RAGE is selectively expressed in neurons from the ischemic penumbra after a focal brain ischemia induced by cortical devascularization. In primary cortical neurons, RAGE expression is induced by excitotoxic glutamate exposure (EGE) and the effects of S100B become potentiated by the previous EGE. In turn, previous S100B exposure protects neurons from hydrogen peroxide induced death. Exposure to 50 nM but not to 1 µM S100B induced NFKB translocation to the nucleus and expression of the NFKB responsive antiapoptotic Bcl-2 gene, an effect potentiated by previous EGE. Chemical blockage of NFKB signalling with sulfasalazine resulted in a dramatic reduction in neuronal survival and both nanomolar and micromolar S100B efficiently protected neurons from NFKB-blockage induced death. These results demonstrated that S100B effects on neurons are modulated by the basal neuronal status. Specifically NFKB activation level and previous exposure to EGE seem to be crucial to determine pro-survival or pro-death S100B effects.