Neuroprotective Factors Secreted by U‐87 Astrocytoma (Astrocytes‐Like) Cells and Their Associated Metabolic Adaptation

Abstract

Astrocytes can and do exert neuroprotective effects on their surrounding neurons both in vivo and in vitro. Our previously observation that U‐87 astrocytoma (astrocytes‐like) cells protect neuroblastoma SK‐N‐SH (neurons‐like) cells against neurodegenerative assaults in co‐cultures prompted us to hypothesize U‐87 cells release neuroprotective factors into the medium and protect neurons by scavenging extracellular glutamate and modulating glutamate‐glutamine cycling. To test this hypothesis, we developed a model using U‐87 cells, stage‐wise deprived them of fetal bovine serum, and then treated them with or without pioglitazone for 24 hours. We then collected the medium (“defined conditioned medium”) the U‐87 cells were in. Then we determined the effects of the media on survival of SK‐N‐SH (neurons‐like) cells. Our results indicated that the survival rates of SK‐N‐SH cells when exposed to the conditioned media were higher than those of untreated SK‐N‐SH cells. We noted U‐87 cells appeared to release glia derived neurotrophic factor (GDNF) into the medium. Moreover, in exerting their protective effect, U‐87 cells seemed to alter their protein expression of glutamine synthetase (GS) and glial fibrillary acidic protein (GFAP) when exposed to various stresses. Thus, the results of our studies further elucidate the mechanisms of neuroprotection of astrocytes‐like U‐87 cells and astrocytes in general.