Animals
Astrocytes/*drug effects/metabolism
Cell Line, Tumor
Estrogen Receptor Modulators/pharmacology
Estrogen Receptor alpha/metabolism
Estrogen Receptor beta/*metabolism
Estrogens/metabolism
Globins/*metabolism
Glucose/*metabolism
Humans
Membrane Potential, Mitochondrial/drug effects
Mice
Nerve Tissue Proteins/*metabolism
Neuroglobin
Norpregnenes/*pharmacology
Protective Agents/*pharmacology
Reactive Oxygen Species/metabolism
Up-Regulation/*drug effects
Tibolone, a synthetic steroid used for the prevention of osteoporosis and the treatment of climacteric symptoms in post-menopausal women, may exert tissue selective estrogenic actions acting on estrogen receptors (ERs). We previously showed that tibolone protects human T98G astroglial cells against glucose deprivation (GD). In this study we have explored whether the protective effect of tibolone on these cells is mediated by ERs. Experimental studies showed that both ERalpha and ERbeta were involved in the protection by tibolone on GD cells, being ERbeta preferentially involved on these actions over ERalpha. Tibolone increased viability of GD cells by a mechanism fully blocked by an ERbeta antagonist and partially blocked by an ERalpha antagonist. Furthermore, ERbeta inhibition prevented the effect of tibolone on nuclear fragmentation, ROS and mitochondrial membrane potential in GD cells. The protective effect of tibolone was mediated by neuroglobin. Tibolone upregulated neuroglobin in T98G cells and primary mouse astrocytes by a mechanism involving ERbeta and neuroglobin silencing prevented the protective action of tibolone on GD cells. In summary, tibolone protects T98G cells by a mechanism involving ERbeta and the upregulation of neuroglobin.Tibolone, a synthetic steroid used for the prevention of osteoporosis and the treatment of climacteric symptoms in post-menopausal women, may exert tissue selective estrogenic actions acting on estrogen receptors (ERs). We previously showed that tibolone protects human T98G astroglial cells against glucose deprivation (GD). In this study we have explored whether the protective effect of tibolone on these cells is mediated by ERs. Experimental studies showed that both ERalpha and ERbeta were involved in the protection by tibolone on GD cells, being ERbeta preferentially involved on these actions over ERalpha. Tibolone increased viability of GD cells by a mechanism fully blocked by an ERbeta antagonist and partially blocked by an ERalpha antagonist. Furthermore, ERbeta inhibition prevented the effect of tibolone on nuclear fragmentation, ROS and mitochondrial membrane potential in GD cells. The protective effect of tibolone was mediated by neuroglobin. Tibolone upregulated neuroglobin in T98G cells and primary mouse astrocytes by a mechanism involving ERbeta and neuroglobin silencing prevented the protective action of tibolone on GD cells. In summary, tibolone protects T98G cells by a mechanism involving ERbeta and the upregulation of neuroglobin.