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 language | English |
|---|---|
| Pages (from-to) | 199-203 |
| Number of pages | 5 |
| Journal | Neuroscience Letters |
| Volume | 612 |
| DOIs | |
| Publication status | Published - 26-01-2016 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Neuroscience(all)
Cite this
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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 journal › Article
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.
UR - http://www.scopus.com/inward/record.url?scp=84955489701&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84955489701&partnerID=8YFLogxK
U2 - 10.1016/j.neulet.2015.12.031
DO - 10.1016/j.neulet.2015.12.031
M3 - Article
C2 - 26708632
AN - SCOPUS:84955489701
VL - 612
SP - 199
EP - 203
JO - Neuroscience Letters
JF - Neuroscience Letters
SN - 0304-3940
ER -