title: Modulating expression of brain heat shock proteins by estrogen in ovariectomized mice model of aging.
abstract: Heat shock proteins (HSPs) serve as molecular chaperones and endogenous cytoprotective factors. Two of the well-studied HSPs, HSP70, and HSP27 can be significantly induced in many areas of brain by a variety of stressors. A decrease in expression of brain HSPs has been documented in aged brain. Estrogen is well known as a neuroprotective hormone, and it has been reported that estrogen can regulate HSP70 and HSP27 expression in neuronal cells. In this study, the relationship between estrogen and heat stress-induced brain HSPs expression in young and aged ovariectomized (OVX) mice was investigated. Our results show that heat stress-induced levels of HSP70 proteins and mRNA transcripts was significantly lower in brain of aged (12 month) OVX mice, compared with young (2 month) OVX mice group. Estrogen supplementation (17beta-estradiol 0.5mg/kg for 7 days) restored heat stress-induced brain HSP70 expression and attenuated heat stress-induced brain DNA fragmentation, caspase 3 activation and mitochondrial leakage of cytochrome c and AIF in OVX mice. These results suggest that estrogen deficiency during aging down-regulates heat stress-induced brain HSP70 expression, which reveals a previously unknown link between estrogen deficiency and stress response elements.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, MD 21201, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Hou
authors.forename: Huailing
authors.initials: H
authors.lastname: Wei
authors.forename: Yuan
authors.initials: Y
authors.lastname: Luo
authors.forename: Gengtao
authors.initials: G
authors.lastname: Liu
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D055551:HSP27 Heat-Shock Proteins / Q000032:analysis* / Q000235:genetics; D018840:HSP70 Heat-Shock Proteins / Q000032:analysis* / Q000235:genetics; D000076249:Heat Shock Transcription Factors; D018869:Heat-Shock Response; D051379:Mice; D008813:Mice, Inbred ICR; D023421:Models, Animal; D010052:Ovariectomy; D012333:RNA, Messenger / Q000032:analysis; D014157:Transcription Factors / Q000096:biosynthesis
chemical_list: D004268:DNA-Binding Proteins; D004967:Estrogens; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; C490017:Hsf1 protein, mouse; C486699:Hspb2 protein, mouse; D012333:RNA, Messenger; D014157:Transcription Factors; D053148:Caspase 3