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The brain activity of heat shock transcription factor 1 (HSF1) is sub‐optimal in estrogen‐ and up‐regulated in testosterone‐treated heat‐shocked rats: Implications for Alzheimer's disease
Author(s) -
Papasozomenos Sozos Ch.,
Papasozomenos Harry
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a73-a
Subject(s) - hsf1 , medicine , endocrinology , testosterone propionate , heat shock factor , chemistry , heat shock protein , hsp70 , biology , microbiology and biotechnology , androgen , biochemistry , hormone , gene
One hundred and fifteen Spraque‐Dawley rats were ovariectomized, given daily injections of 10 μg of 17β‐estradiol 3‐benzoate (EB), or 250 μg of testosterone propionate (TP), or 10 μg of EB + 250 μg of TP or sesame oil for 4–8 wk, and heat shocked at 42°C for 15 min. At 0 h after heat shock, HSF1 was least and most inducibly hyperphosphorylated (pHSF1) in the EB ‐ and TP‐treated rats, respectively, and accumulated in the nucleus except in the EB ‐treated group. Also, while the subnuclear distribution of HSF1 was similar in control and heat‐shocked EB‐treated rats, it localized exclusively on euchromatin in heat‐shocked TP‐treated rats. Synthesis of the heat shock‐induced protein Hsp70 was lowest in EB‐ and highest in TP‐treated rats. A mAb whose epitope maps with the autorepressive heptad repeat of HSF1 and contains the consensus motif SNLD for protein kinase CK2, preferentially recognized pHSF1 and stained exclusively nuclei. In this rat heat shock model, TP prevents the overactivation of glycogen synthase kinase‐3β, known to phosphorylate and repress HSF1, and abolishes the hyperphosphorylation of tau protein [ Papasozomenos, S. C., and Shanavas, A. (2002) Proc. Natl. Acad. Sci. USA 99 , –1145 ]. Because recent studies suggest a beneficial role of HSF1 in delaying aging and preventing Alzheimer's disease (AD), the up‐regulation of its activity by TP makes the argument for using androgens in preventing AD more compelling.