Unfolded protein response in hypothalamic cultures of wild-type and ATF6α-knockout mice

Wenjun Lu, Daisuke Hagiwara, Yoshiaki Morishita, Masayoshi Tochiya, Yoshinori Azuma, Hidetaka Suga, Motomitsu Goto, Ryoichi Banno, Yoshihisa Sugimura, Seiichi Oyadomari, Kazutoshi Mori, Hiroshi Arima

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)199-203
Number of pages5
JournalNeuroscience Letters
Volume612
DOIs
Publication statusPublished - 26-01-2016
Externally publishedYes

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Activating Transcription Factor 6
Unfolded Protein Response
Endoplasmic Reticulum Stress
Transcription Factor CHOP
Knockout Mice
Activating Transcription Factor 4
Endoplasmic Reticulum
Thapsigargin
Hypothalamus
Endoplasmic Reticulum-Associated Degradation
Recombinant DNA
Protein C
Transducers
Carrier Proteins
Up-Regulation
Messenger RNA
Water

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Lu, W., Hagiwara, D., Morishita, Y., Tochiya, M., Azuma, Y., Suga, H., ... Arima, H. (2016). Unfolded protein response in hypothalamic cultures of wild-type and ATF6α-knockout mice. Neuroscience Letters, 612, 199-203. https://doi.org/10.1016/j.neulet.2015.12.031
Lu, Wenjun ; Hagiwara, Daisuke ; Morishita, Yoshiaki ; Tochiya, Masayoshi ; Azuma, Yoshinori ; Suga, Hidetaka ; Goto, Motomitsu ; Banno, Ryoichi ; Sugimura, Yoshihisa ; Oyadomari, Seiichi ; Mori, Kazutoshi ; Arima, Hiroshi. / Unfolded protein response in hypothalamic cultures of wild-type and ATF6α-knockout mice. In: Neuroscience Letters. 2016 ; Vol. 612. pp. 199-203.
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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.",
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Lu, W, Hagiwara, D, Morishita, Y, Tochiya, M, Azuma, Y, Suga, H, Goto, M, Banno, R, Sugimura, Y, Oyadomari, S, Mori, K & Arima, H 2016, 'Unfolded protein response in hypothalamic cultures of wild-type and ATF6α-knockout mice', Neuroscience Letters, vol. 612, pp. 199-203. https://doi.org/10.1016/j.neulet.2015.12.031

Unfolded protein response in hypothalamic cultures of wild-type and ATF6α-knockout mice. / Lu, Wenjun; Hagiwara, Daisuke; Morishita, Yoshiaki; Tochiya, Masayoshi; Azuma, Yoshinori; Suga, Hidetaka; Goto, Motomitsu; Banno, Ryoichi; Sugimura, Yoshihisa; Oyadomari, Seiichi; Mori, Kazutoshi; Arima, Hiroshi.

In: Neuroscience Letters, Vol. 612, 26.01.2016, p. 199-203.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Unfolded protein response in hypothalamic cultures of wild-type and ATF6α-knockout mice

AU - Lu, Wenjun

AU - Hagiwara, Daisuke

AU - Morishita, Yoshiaki

AU - Tochiya, Masayoshi

AU - Azuma, Yoshinori

AU - Suga, Hidetaka

AU - Goto, Motomitsu

AU - Banno, Ryoichi

AU - Sugimura, Yoshihisa

AU - Oyadomari, Seiichi

AU - Mori, Kazutoshi

AU - Arima, Hiroshi

PY - 2016/1/26

Y1 - 2016/1/26

N2 - 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.

AB - 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.

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