title: Ovariectomy and 17β-estradiol replacement play a role on the expression of Endonuclease-G and phosphorylated cyclic AMP response element-binding (CREB) protein in hippocampus.
abstract: The aim of the present study was to investigate the effects of different periods of ovariectomy and 17β-estradiol (E2) replacement on the expression of Cytochrome C, apoptosis inducing factor (AIF) and Endonuclease-G (Endo-G) in mitochondrial and cytosolic fractions obtained from hippocampus of the adult female rats. In addition, the expression of phosphorylated CREB (phospho-CREB) was also analyzed in hippocampus. Ovariectomy or E2 treatment did not change the expression of Cytochrome C and AIF. Ovariectomy (15, 21 and 36 days) decreased the expression of Endo-G in the mitochondrial fractions and increased it in the cytosolic fractions obtained from hippocampus. The treatment with E2 after 15 days of ovariectomy for 7 days or 21 days, and throughout the post-ovariectomy period prevented the effects of ovariectomy on Endo-G expression. Our results suggest that ovariectomy-induced apoptotic cell death in hippocampal tissue could be mediated by Endo-G, but not by AIF, via a caspase-independent apoptotic pathway. Furthermore, ovariectomy decreased the expression of phospho-CREB and the treatment with E2 prevented these effects. In conclusion, E2 may help maintain long-term neuronal viability by regulating the expression of members of the Bcl-2 family. Regulation of Endo-G released from mitochondria, but not of Cytochrome C and AIF, is also involved in the neuroprotective actions of E2. Furthermore, CREB may be involved in the expression of Bcl-2. These data provide new understanding into the mechanisms involved in the neuroprotective role of estrogen.
authors.affiliation: Laboratory of Pharmacology, Instituto Butantan, São Paulo, Brazil.
authors.forename: Renato Tavares
authors.initials: RT
authors.lastname: Dos Santos Pereira
authors.affiliation: Section of Experimental Endocrinology, Department of Pharmacology, Escola Paulista de Medicina-Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Catarina Segreti
authors.initials: CS
authors.lastname: Porto
authors.affiliation: Laboratory of Pharmacology, Instituto Butantan, São Paulo, Brazil. Electronic address: fernando.abdalla@butantan.gov.br.
authors.forename: Fernando Maurício Francis
authors.initials: FMF
authors.lastname: Abdalla
mesh_terms: D000818:Animals; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D045304:Cytochromes c / Q000378:metabolism; D004706:Endodeoxyribonucleases / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology*; D015914:Estrogen Replacement Therapy; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D010052:Ovariectomy; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
chemical_list: D051033:Apoptosis Inducing Factor; D017362:Cyclic AMP Response Element-Binding Protein; D004958:Estradiol; D045304:Cytochromes c; D004706:Endodeoxyribonucleases; C052391:endonuclease G
keywords: 17β-Estradiol; AIF; CREB; Cytochrome C; Endonuclease-G; Hippocampus