title: Unfolded protein response in hypothalamic cultures of wild-type and ATF6α-knockout mice.
abstract: Recent studies suggest that endoplasmic reticulum (ER) stress in the hypothalamus could affect systemic homeostatic regulation in areas such as energy and water balance. Activating transcription factor 6α (ATF6α) is an ER stress transducer which increases the expression of ER chaperones and ER-associated degradation (ERAD) components under ER stress. In the present study, we examined the regulation of the unfolding protein response (UPR) in mouse hypothalamic cultures of wild-type (WT) and ATF6α(-/-) mice. Thapsigargin (TG), an ER stressor, significantly increased the mRNA expression of immunoglobulin heavy chain binding protein (BiP), spliced X-box binding protein 1 (XBP1), activating transcription factor 4 (ATF4), C/EBP homologous protein (CHOP), and ERAD components, in hypothalamic cultures of WT mice with the same threshold (0.1μM) and similar time courses. On the other hand, TG-induced upregulation of BiP and CHOP as well as most ERAD-related genes, but not spliced XBP1 or ATF4, was attenuated in ATF6α(-/-) mice compared with WT mice. Our data suggest that all the UPR arms are activated similarly in the mouse hypothalamus under ER stress conditions, where ATF6α regulates the expression of ER chaperones, CHOP, and ERAD components.
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Lu
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan. Electronic address: d-hagiwara@med.nagoya-u.ac.jp.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Hagiwara
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan. Electronic address: yoshi214@med.nagoya-u.ac.jp.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Morishita
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Tochiya
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Azuma
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Suga
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Motomitsu
authors.initials: M
authors.lastname: Goto
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Banno
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Sugimura
authors.affiliation: Institute for Genome Research, University of Tokushima, Tokushima 770-8503, Japan.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Oyadomari
authors.affiliation: Department of Biophysics, Graduate School of Science, Kyoto University, Kyoto 606-8502, Japan.
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Mori
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan. Electronic address: arima105@med.nagoya-u.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Arima
mesh_terms: D051702:Activating Transcription Factor 6 / Q000235:genetics*; D000818:Animals; D059865:Endoplasmic Reticulum Stress; D007031:Hypothalamus / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D019284:Thapsigargin / Q000494:pharmacology; D013997:Time Factors; D046509:Tissue Culture Techniques; D056811:Unfolded Protein Response
chemical_list: D051702:Activating Transcription Factor 6; C574724:Atf6b protein, mouse; D019284:Thapsigargin
keywords: Activating transcription factor 6α (ATF6α); Endoplasmic reticulum (ER) stress; Endoplasmic reticulum-associated degradation (ERAD); Hypothalamus; Unfolded protein response (UPR)