PMID- 23994062 OWN - NLM STAT- MEDLINE DCOM- 20140508 LR - 20131007 IS - 1872-7972 (Electronic) IS - 0304-3940 (Linking) VI - 553 DP - 2013 Oct 11 TI - Expression of neuropeptide Y and agouti-related protein mRNA stimulated by glucocorticoids is attenuated via NF-kappaB p65 under ER stress in mouse hypothalamic cultures. PG - 165-9 LID - S0304-3940(13)00773-8 [pii] LID - 10.1016/j.neulet.2013.08.040 [doi] AB - There are several lines of evidence suggesting that glucocorticoid signaling in the hypothalamus plays an important role in energy balance, and recent studies suggest that endoplasmic reticulum (ER) stress in the hypothalamus could affect signaling related to energy balance. In the present study, we examined the regulation of glucocorticoid signaling under ER stress in mouse hypothalamic organotypic cultures. Incubation of the hypothalamic explants with dexamethasone (DEX) significantly increased expression levels of neuropeptide Y (NPY) and agouti-related protein (AgRP) mRNA, and treatment with thapsigargin (TG), an ER stressor, significantly attenuated DEX-induced NPY and AgRP mRNA expression. TG treatment increased the levels of phospho-NF-kappaB p65 in hypothalamic cultures, and inhibitors of NF-kappaB p65 reversed the inhibitory effects of TG on NPY and AgRP expression. Our data thus demonstrated that glucocorticoid-stimulated NPY and AgRP expression was attenuated via NF-kappaB p65 pathways under ER stress, and suggest crosstalk between ER stress and inflammation in the hypothalamus. CI - Copyright (c) 2013 Elsevier Ireland Ltd. All rights reserved. FAU - Hagimoto, Shigeru AU - Hagimoto S AD - Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan. FAU - Arima, Hiroshi AU - Arima H FAU - Adachi, Koichi AU - Adachi K FAU - Ito, Yoshihiro AU - Ito Y FAU - Suga, Hidetaka AU - Suga H FAU - Sugimura, Yoshihisa AU - Sugimura Y FAU - Goto, Motomitsu AU - Goto M FAU - Banno, Ryoichi AU - Banno R FAU - Oiso, Yutaka AU - Oiso Y LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130828 PL - Ireland TA - Neurosci Lett JT - Neuroscience letters JID - 7600130 RN - 0 (Agouti-Related Protein) RN - 0 (Glucocorticoids) RN - 0 (Neuropeptide Y) RN - 0 (RNA, Messenger) RN - 0 (Transcription Factor RelA) RN - 67526-95-8 (Thapsigargin) RN - 7S5I7G3JQL (Dexamethasone) SB - IM MH - Agouti-Related Protein/genetics/*metabolism MH - Animals MH - Dexamethasone/pharmacology MH - *Endoplasmic Reticulum Stress MH - Glucocorticoids/pharmacology/*physiology MH - Hypothalamus/*drug effects/metabolism MH - Mice MH - Mice, Inbred C57BL MH - Neuropeptide Y/genetics/*metabolism MH - RNA, Messenger/*metabolism MH - Signal Transduction MH - Thapsigargin/pharmacology MH - Tissue Culture Techniques MH - Transcription Factor RelA/*metabolism OTO - NOTNLM OT - AgRP OT - Agouti-related proteins OT - DEX OT - ER OT - Endoplasmic reticulum stress OT - GR OT - Glucocorticoids OT - NF-kappaB OT - NPY OT - Neuropeptide Y OT - TG OT - TN OT - UPR OT - agouti-related protein OT - dexamethasone OT - endoplasmic reticulum OT - glucocorticoid receptor OT - neuropeptide Y OT - p38 MAPK OT - p38 mitogen-activated protein kinases OT - thapsigargin OT - tunicamycin OT - unfolded protein response EDAT- 2013/09/03 06:00 MHDA- 2014/05/09 06:00 CRDT- 2013/09/03 06:00 PHST- 2013/06/08 00:00 [received] PHST- 2013/08/07 00:00 [revised] PHST- 2013/08/20 00:00 [accepted] PHST- 2013/09/03 06:00 [entrez] PHST- 2013/09/03 06:00 [pubmed] PHST- 2014/05/09 06:00 [medline] AID - S0304-3940(13)00773-8 [pii] AID - 10.1016/j.neulet.2013.08.040 [doi] PST - ppublish SO - Neurosci Lett. 2013 Oct 11;553:165-9. doi: 10.1016/j.neulet.2013.08.040. Epub 2013 Aug 28.