title: Expression of neuropeptide Y and agouti-related protein mRNA stimulated by glucocorticoids is attenuated via NF-κB p65 under ER stress in mouse hypothalamic cultures.
abstract: 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-κB p65 in hypothalamic cultures, and inhibitors of NF-κB 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-κB p65 pathways under ER stress, and suggest crosstalk between ER stress and inflammation in the hypothalamus.
authors.affiliation: Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Hagimoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Arima
authors.forename: Koichi
authors.initials: K
authors.lastname: Adachi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ito
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Suga
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Sugimura
authors.forename: Motomitsu
authors.initials: M
authors.lastname: Goto
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Banno
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Oiso
mesh_terms: D054369:Agouti-Related Protein / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology; D059865:Endoplasmic Reticulum Stress; D005938:Glucocorticoids / Q000494:pharmacology / Q000502:physiology*; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D015398:Signal Transduction; D019284:Thapsigargin / Q000494:pharmacology; D046509:Tissue Culture Techniques; D051996:Transcription Factor RelA / Q000378:metabolism*
chemical_list: D054369:Agouti-Related Protein; D005938:Glucocorticoids; D009478:Neuropeptide Y; D012333:RNA, Messenger; D051996:Transcription Factor RelA; D019284:Thapsigargin; D003907:Dexamethasone
keywords: AgRP; Agouti-related proteins; DEX; ER; Endoplasmic reticulum stress; GR; Glucocorticoids; NF-κB; NPY; Neuropeptide Y; TG; TN; UPR; agouti-related protein; dexamethasone; endoplasmic reticulum; glucocorticoid receptor; neuropeptide Y; p38 MAPK; p38 mitogen-activated protein kinases; thapsigargin; tunicamycin; unfolded protein response