Unfolded protein response in hypothalamic cultures of wild-type and ATF6 alpha-knockout mice

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

来源：Neuroscience Letters, 2016, 612: 199-203.

DOI：10.1016/j.neulet.2015.12.031

• Activating transcription factor 6 alpha (ATF6 alpha)
• Hypothalamus
• Endoplasmic reticulum (ER) stress
• Unfolded protein response (UPR)
• Endoplasmic reticulum-associated degradation (ERAD)

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 6 alpha (ATF6 alpha) 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 ATF6 alpha(-/-) 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), MEP homologous protein (CHOP), and ERAD components, in hypothalamic cultures of WT mice with the same threshold (0.1 mu M) 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 ATF6 alpha(-/-) 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 ATF6 alpha regulates the expression of ER chaperones, CHOP, and ERAD components.

• 出版日期2016-1-26