| http://purl.uniprot.org/citations/25183803 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/25183803 | http://www.w3.org/2000/01/rdf-schema#comment | "Evidence suggests a causative role for endoplasmic reticulum (ER) stress in the development of atherosclerosis. This study investigated the potential role of glycogen synthase kinase (GSK)-3α/β in proatherogenic ER stress signaling. Thp1-derived macrophages were treated with the ER stress-inducing agents, glucosamine, thapsigargin, or palmitate. Using small-molecule inhibitors of specific unfolded protein response (UPR) signaling pathways, we found that protein kinase R-like ER kinase (PERK), but not inositol requiring enzyme 1 or activating transcription factor 6, is required for the activation of GSK3α/β by ER stress. GSK3α/β inhibition or siRNA-directed knockdown attenuated ER stress-induced expression of distal components of the PERK pathway. Macrophage foam cells within atherosclerotic plaques and isolated macrophages from ApoE(-/-) mice fed a diet supplemented with the GSK3α/β inhibitor valproate had reduced levels of C/EBP homologous protein (CHOP). GSK3α/β inhibition blocked ER stress-induced lipid accumulation and the upregulation of genes associated with lipid metabolism. In primary mouse macrophages, PERK inhibition blocked ER stress-induced lipid accumulation, whereas constitutively active S9A-GSK3β promoted foam cell formation and CHOP expression, even in cells treated with a PERK inhibitor. These findings suggest that ER stress-PERK-GSK3α/β signaling promotes proatherogenic macrophage lipid accumulation."xsd:string |
| http://purl.uniprot.org/citations/25183803 | http://purl.org/dc/terms/identifier | "doi:10.1194/jlr.m051094"xsd:string |
| http://purl.uniprot.org/citations/25183803 | http://purl.uniprot.org/core/author | "Werstuck G.H."xsd:string |
| http://purl.uniprot.org/citations/25183803 | http://purl.uniprot.org/core/author | "McAlpine C.S."xsd:string |
| http://purl.uniprot.org/citations/25183803 | http://purl.uniprot.org/core/date | "2014"xsd:gYear |
| http://purl.uniprot.org/citations/25183803 | http://purl.uniprot.org/core/name | "J Lipid Res"xsd:string |
| http://purl.uniprot.org/citations/25183803 | http://purl.uniprot.org/core/pages | "2320-2333"xsd:string |
| http://purl.uniprot.org/citations/25183803 | http://purl.uniprot.org/core/title | "Protein kinase R-like endoplasmic reticulum kinase and glycogen synthase kinase-3alpha/beta regulate foam cell formation."xsd:string |
| http://purl.uniprot.org/citations/25183803 | http://purl.uniprot.org/core/volume | "55"xsd:string |
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