| http://purl.uniprot.org/citations/16407292 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/16407292 | http://www.w3.org/2000/01/rdf-schema#comment | "Familial autosomal dominant hypercholesterolemia is associated with high risk for cardiovascular accidents and is related to mutations in the low density lipoprotein receptor or its ligand apolipoprotein B (apoB). Mutations in a third gene, proprotein convertase subtilisin kexin 9 (PCSK9), were recently associated to this disease. PCSK9 acts as a natural inhibitor of the low density lipoprotein receptor pathway, and both genes are regulated by depletion of cholesterol cell content and statins, via sterol regulatory element-binding protein (SREBP). Here we investigated the regulation of PCSK9 gene expression during nutritional changes. We showed that PCSK9 mRNA quantity is decreased by 73% in mice after 24 h of fasting, leading to a 2-fold decrease in protein level. In contrast PCSK9 expression was restored upon high carbohydrate refeeding. PCSK9 mRNA increased by 4-5-fold in presence of insulin in rodent primary hepatocytes, whereas glucose had no effect. Moreover, insulin up-regulated hepatic PCSK9 expression in vivo during a hyperinsulinemic-euglycemic clamp in mice. Adenoviral mediated overexpression of a dominant or negative form of SREBP-1c confirmed the implication of this transcription factor in insulin-mediated stimulation of PCSK9 expression. Liver X receptor agonist T0901317 also regulated PCSK9 expression via this same pathway (a 2-fold increase in PCSK9 mRNA of primary hepatocytes cultured for 24 h in presence of 1 microm T0901317). As our last investigation, we isolated PCSK9 proximal promoter and verified the functionality of a SREBP-1c responsive element located from 335 bp to 355 bp upstream of the ATG. Together, these results show that PCSK9 expression is regulated by nutritional status and insulinemia."xsd:string |
| http://purl.uniprot.org/citations/16407292 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m508582200"xsd:string |
| http://purl.uniprot.org/citations/16407292 | http://purl.uniprot.org/core/author | "Lambert G."xsd:string |
| http://purl.uniprot.org/citations/16407292 | http://purl.uniprot.org/core/author | "Costet P."xsd:string |
| http://purl.uniprot.org/citations/16407292 | http://purl.uniprot.org/core/author | "Krempf M."xsd:string |
| http://purl.uniprot.org/citations/16407292 | http://purl.uniprot.org/core/author | "Staels B."xsd:string |
| http://purl.uniprot.org/citations/16407292 | http://purl.uniprot.org/core/author | "Cariou B."xsd:string |
| http://purl.uniprot.org/citations/16407292 | http://purl.uniprot.org/core/author | "Grefhorst A."xsd:string |
| http://purl.uniprot.org/citations/16407292 | http://purl.uniprot.org/core/author | "Lardeux B."xsd:string |
| http://purl.uniprot.org/citations/16407292 | http://purl.uniprot.org/core/author | "Lalanne F."xsd:string |
| http://purl.uniprot.org/citations/16407292 | http://purl.uniprot.org/core/author | "Jarnoux A.L."xsd:string |
| http://purl.uniprot.org/citations/16407292 | http://purl.uniprot.org/core/date | "2006"xsd:gYear |
| http://purl.uniprot.org/citations/16407292 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/16407292 | http://purl.uniprot.org/core/pages | "6211-6218"xsd:string |
| http://purl.uniprot.org/citations/16407292 | http://purl.uniprot.org/core/title | "Hepatic PCSK9 expression is regulated by nutritional status via insulin and sterol regulatory element-binding protein 1c."xsd:string |
| http://purl.uniprot.org/citations/16407292 | http://purl.uniprot.org/core/volume | "281"xsd:string |
| http://purl.uniprot.org/citations/16407292 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/16407292 |
| http://purl.uniprot.org/citations/16407292 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/16407292 |
| http://purl.uniprot.org/uniprot/Q8NBP7#attribution-E2345FD45079570DCB72FBB631A81351 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/16407292 |
| http://purl.uniprot.org/uniprot/Q80W65#attribution-6FC0F6643458A96DFE13E41CB724FC2A | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/16407292 |
| http://purl.uniprot.org/uniprot/P59996#attribution-6FC0F6643458A96DFE13E41CB724FC2A | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/16407292 |
| http://purl.uniprot.org/uniprot/Q9WTN3#attribution-6FC0F6643458A96DFE13E41CB724FC2A | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/16407292 |
| http://purl.uniprot.org/uniprot/Q9WTN3#attribution-E2345FD45079570DCB72FBB631A81351 | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/16407292 |
| http://purl.uniprot.org/uniprot/P36956#attribution-6FC0F6643458A96DFE13E41CB724FC2A | http://purl.uniprot.org/core/source | http://purl.uniprot.org/citations/16407292 |