title: Tibolone protects astrocytic cells from glucose deprivation through a mechanism involving estrogen receptor beta and the upregulation of neuroglobin expression.
abstract: 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 ERα and ERβ were involved in the protection by tibolone on GD cells, being ERβ preferentially involved on these actions over ERα. Tibolone increased viability of GD cells by a mechanism fully blocked by an ERβ antagonist and partially blocked by an ERα antagonist. Furthermore, ERβ 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 ERβ and neuroglobin silencing prevented the protective action of tibolone on GD cells. In summary, tibolone protects T98G cells by a mechanism involving ERβ and the upregulation of neuroglobin.
authors.affiliation: Departamento de Nutrición y Bioquímica, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá, D.C., Colombia; Departamento de Ciencias Clínicas, Facultad de Ciencias de la Salud, Universidad del Tolima, Ibagué, Colombia.
authors.forename: Marco
authors.initials: M
authors.lastname: Avila-Rodriguez
authors.affiliation: Instituto Cajal, CSIC, Avenida Doctor Arce 37, 28002, Madrid, Spain. Electronic address: lmgs@cajal.csic.es.
authors.forename: Luis Miguel
authors.initials: LM
authors.lastname: Garcia-Segura
authors.affiliation: Departamento de Nutrición y Bioquímica, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá, D.C., Colombia.
authors.forename: Oscar
authors.initials: O
authors.lastname: Hidalgo-Lanussa
authors.affiliation: Departamento de Nutrición y Bioquímica, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá, D.C., Colombia.
authors.forename: Eliana
authors.initials: E
authors.lastname: Baez
authors.affiliation: Departamento de Nutrición y Bioquímica, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá, D.C., Colombia.
authors.forename: Janneth
authors.initials: J
authors.lastname: Gonzalez
authors.affiliation: Departamento de Nutrición y Bioquímica, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá, D.C., Colombia; Instituto de Ciencias Biomédicas, Universidad Autónoma de Chile, Santiago, Chile; Universidad Científica del Sur, Lima, Peru. Electronic address: gsampaio@javeriana.edu.co.
authors.forename: George E
authors.initials: GE
authors.lastname: Barreto
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D045744:Cell Line, Tumor; D020847:Estrogen Receptor Modulators / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism; D005914:Globins / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D000078787:Neuroglobin; D009652:Norpregnenes / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D020847:Estrogen Receptor Modulators; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D009419:Nerve Tissue Proteins; D000078787:Neuroglobin; D009652:Norpregnenes; D020011:Protective Agents; D017382:Reactive Oxygen Species; D005914:Globins; C027385:tibolone; D005947:Glucose
keywords: Astrocytes; ERβ; Glucose deprivation; Mitochondria; Neuroglobin; Tibolone