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

Neuroscience letters 2016 Jan 26

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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. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Citation

Wenjun Lu, Daisuke Hagiwara, Yoshiaki Morishita, Masayoshi Tochiya, Yoshinori Azuma, Hidetaka Suga, Motomitsu Goto, Ryoichi Banno, Yoshihisa Sugimura, Seiichi Oyadomari, Kazutoshi Mori, Hiroshi Arima. Unfolded protein response in hypothalamic cultures of wild-type and ATF6α-knockout mice. Neuroscience letters. 2016 Jan 26;612:199-203