Peer-Reviewed Journal Details
Mandatory Fields
Avila-Rodriguez, M.,Garcia-Segura, L. M.,Hidalgo-Lanussa, O.,Baez, E.,Gonzalez, J.,Barreto, G. E.
2016
September
Mol Cell Endocrinolmol Cell Endocrinol
Tibolone protects astrocytic cells from glucose deprivation through a mechanism involving estrogen receptor beta and the upregulation of neuroglobin expression
Published
()
Optional Fields
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
433
35
46
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.
1872-8057 (Electronic) 03
2016/06/03
http://www.ncbi.nlm.nih.gov/pubmed/27250720http://www.ncbi.nlm.nih.gov/pubmed/27250720
10.1016/j.mce.2016.05.024
Grant Details