Showing papers on "Transcription Factor CHOP published in 2020"
TL;DR: It is suggested that free fatty acids may be involved in the control of GDF-15 and provide new molecular insights about how diet and lipid metabolism may regulate the development of obesity and T2D.
Abstract: Growth differentiation factor-15 (GDF-15) and its receptor GFRAL are both involved in the development of obesity and insulin resistance. Plasmatic GDF-15 level increases with obesity and is positively associated with disease progression. Despite macrophages have been recently suggested as a key source of GDF-15 in obesity, little is known about the regulation of GDF-15 in these cells. In the present work, we sought for potential pathophysiological activators of GDF15 expression in human macrophages and identified saturated fatty acids (SFAs) as strong inducers of GDF15 expression and secretion. SFAs increase GDF15 expression through the induction of an ER stress and the activation of the PERK/eIF2/CHOP signaling pathway in both PMA-differentiated THP-1 cells and in primary monocyte-derived macrophages. The transcription factor CHOP directly binds to the GDF15 promoter region and regulates GDF15 expression. Unlike SFAs, unsaturated fatty acids do not promote GDF15 expression and rather inhibit both SFA-induced GDF15 expression and ER stress. These results suggest that free fatty acids may be involved in the control of GDF-15 and provide new molecular insights about how diet and lipid metabolism may regulate the development of obesity and T2D.
12 citations
TL;DR: Elevated levels of NF-YA, as found in some tumor types, helps altering cancer metabolic pathways, and Elevated basal levels of SERCA1/2, coding for the molecular target of Thapsigargin, correlate with resistance ofNF-YA OE cells to the drug.
6 citations
TL;DR: NOD2 specifically interacted with ER stress sensor activating transcription factor 6 (ATF6) and suppressed the expression of proapoptotic transcription factor CHOP (C/EBP homologous protein) during ER stress, indicating an unsuspected critical role for NOD2 in ER stress‐induced cell death.
Abstract: Endoplasmic reticulum (ER) stress-induced cell death of vascular smooth muscle cells (VSMCs) is extensively involved in atherosclerotic plaque stabilization. We previously reported that nucleotide-binding oligomerization domain protein 2 (NOD2) participated in vascular homeostasis and tissue injury. However, the role and underlying mechanisms of NOD2 remain unknown in ER stress-induced cell death of VSMC during vascular diseases, including advanced atherosclerosis. Here, we report that NOD2 specifically interacted with ER stress sensor activating transcription factor 6 (ATF6) and suppressed the expression of proapoptotic transcription factor CHOP (C/EBP homologous protein) during ER stress. CHOP-positive cells were increased in neointimal lesions after femoral artery injury in NOD2-deficient mice. In particular, a NOD2 ligand, MDP, and overexpression of NOD2 decreased CHOP expression in wild-type VSMCs. NOD2 interacted with an ER stress sensor molecule, ATF6, and acted as a negative regulator for ATF6 activation and its downstream target molecule, CHOP, that regulates ER stress-induced apoptosis. Moreover, NOD2 deficiency promoted disruption of advanced atherosclerotic lesions and CHOP expression in NOD2-/- ApoE-/- mice. Our findings indicate an unsuspected critical role for NOD2 in ER stress-induced cell death.
2 citations