EC Number   |
Expression |
Reference |
|---|
   3.4.21.61 | down |
cholesterol (0.1 mM) solubilized in albumin or micelles significantly downregulates PCSK9 gene (30%) and protein expression (50%) in Caco-2/15 cells. Cells treated with 25-hydroxycholesterol (0.05 mM) also display significant reduction in PCSK9 gene (37%) and protein (75%) expression. Addition of bile acids taurocholate and deoxycholate to the apical culture medium lowers PCSK9 gene expression (25%) and raises PCSK9 protein expression (30%), respectively, probably via the modulation of farnesoid X receptor |
707063 |
| 3.4.21.61 | down |
cholesteryl ester transfer protein inhibitors downregulate PCSK9 and LDLR expression through decreases in SREBP2 expression in hepatocytes. Glitazones, rapamycine, berberine, and resistin cause a reduction of enzyme expression via HNF1alpha reduction. Reduction of enzyme expression can be achieved by peroxisome proliferator-activated receptor alpha and activation of sterolresponse element binding protein 2. In HepG2 cells, hyperinsulinemia decreases the enzyme expression, an effect which is also observed in post-menopausal obese women |
731241 |
| 3.4.21.61 | down |
knockdown of PCSK9 expression in immortalized human hepatocytes using specific siRNA which results in a 38% and 53% decrease in PCSK9 protein quantity, respectively in cell lysates and culture media compared with controls |
707332 |
| 3.4.21.61 | more |
in healthy men 24 h hyperinsulinemia does not alter plasma the enzyme concentrations, and the enzyme expression is similar in normal, pre- and Typ2-diabetic patients |
731241 |
| 3.4.21.61 | up |
amounts of PCSK9 mRNA and protein in Caco-2/15 cells are associated to the regulation of 3-hydroxy-3-methylglutaryl-CoA reductase and sterol regulatory element binding protein-2 that can transcriptionally activate PCSK9 via sterol-regulatory elements located in its proximal promoter region. Depletion of cholesterol content by hydroxypropyl-beta-cyclodextrin upregulates PCSK9 transcripts (20%) and protein mass (540%), in parallel with sterol regulatory element binding protein-2 protein levels |
707063 |
| 3.4.21.61 | up |
PCSK9 is expressed throughout the entire small intestine and in enterocytes. PCSK9 is expressed almost exclusively in the epithelial barrier of the duodenum and ileum, both in enterocytes and goblet cells. PCSK9 is 160% upregulated by 0.01 mM pravastatin in CaCo-2 cells after exposure for 48 h |
707305 |
| 3.4.21.61 | up |
PCSK9 is expressed throughout the small intestine and colon, at a level which does not vary significantly along the intestinal cephalo-caudal axis, and which is similar to that in the liver |
707305 |
| 3.4.21.61 | up |
PCSK9 levels correlate with plasma cholesterol, LDL-C, triglycerides, fasting glucose, age and body mass index. In hypercholesterolemic patients, circulating PCSK9 is higher than in healthy volunteers, and increases with increasing statin dose, and further increased when ezetimibe is added. Ezetimibe treatment of Hep-G2 (hepatocytes) and Caco-2 (enterocytes) cells causes a slight increase in PCSK9 mRNA, but no significant rise in PCSK9 protein secretion, suggesting that these transformed cells are not ideal model cell lines |
710641 |
| 3.4.21.61 | up |
the enzyme is up-regulated during apoptosis of neurons. Statins and increase the transcription factor SREBP2, statins also the HNF1alpha expression, and fibrates increase PPAralpha, all leading to increased enzyme PCSK9 expression. Activation of enzyme expression can be mediated by activation of insulin receptors and subsequent activation of the sterolresponse element binding protein 1 and mammalian target of rapamycin pathways |
731241 |
