کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5534301 1550840 2017 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
LUMAN/CREB3 is a key regulator of glucocorticoid-mediated stress responses
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
LUMAN/CREB3 is a key regulator of glucocorticoid-mediated stress responses
چکیده انگلیسی


- Luman-deficient mice exhibit a blunted stress response.
- Luman deficiency results in increased glucocorticoid receptor (GR) activity.
- Lower corticosterone levels were observed in Luman-deficient mice.
- With elevated GR, dendritic branching is reduced in the hippocampal CA3 region.
- LUMAN is a key regulator of GR-mediated signaling and modulates HPA axis reactivity.

Altered glucocorticoid sensitivity is believed to contribute to a number of human diseases, including inflammatory and autoimmune conditions as well as disorders characterized by abnormal hypothalamic-pituitary-adrenal axis (HPA) function. LUMAN (or CREB3), originally identified through its interaction with a cell cycle regulator HCFC1, is an endoplasmic reticulum membrane-bound transcription factor that is involved in the unfolded protein response. Here we demonstrate that LUMAN changes the glucocorticoid response by modulating the expression of the glucocorticoid receptor leading to an overall increase in GR activity. Luman-deficient mice exhibited a blunted stress response characterized by low levels of both anxiety and depressive-like behaviour in addition to low circulating corticosterone levels. These mice also have reduced dendritic branching in the CA3 region of the hippocampus, consistent with increased GR responses. These findings are consistent with the notion that elevated GR activities are the primary cause of the observed phenotype in these LUMAN-deficient mice. We thus postulate that LUMAN is a key regulator of GR-mediated signaling and modulates HPA axis reactivity.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular and Cellular Endocrinology - Volume 439, 5 January 2017, Pages 95-104
نویسندگان
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