CircuLex Mouse/Rat PCSK9 ELISA Kit

  • Applications
    • ELISA
  • Code # CY-8078
  • Size 96 Assays
  • Price
    $540.75
Specifications

Background

PCSK9 (also known as neural apoptosis-regulated convertase, NARC-1) is a 692-residue extracellular protein expressed primarily in the kidneys, liver and intestines (1) representing the 9th member of the secretory subtilase family. Various genetic observations subsequently mapped PCSK9 as the third gene (along with LDLR and APOB) to cause autosomal dominant hypercholesterolemia (ADH). These studies suggested that gain of function mutations increase plasma levels of LDL-c (2–6), whereas nonsense or missense (loss-of-function) mutations, which interfere with folding or secretion of PCSK9, lead to a reduction of plasma levels of LDL-c and an 88% decrease in the risk of coronary heart disease (CHD) (5). In mice, adenoviral overexpression of PCSK9 results in increased plasma LDL-c level in normal mice but not in LDLR-deficient mice (7). Deletion of PCSK9 causes an increase in level of LDLR protein but not mRNA (8). These findings lead to a hypothesis that PCSK9 exerts its role in cholesterol metabolism through posttranslational down-regulation of LDLR, the receptor responsible for clearing LDL-c from plasma. Evidence is consistent with the secreted form of PCSK9 binding directly to the LDLR and resulting in degradation of the receptor (9, 10). Zhang et al. (11) localized the binding site of PCSK9 in the LDLR to the first epidermal growth factor-like repeat (EGF-A) of the extracellular domain and showed that PCSK9 binding to this site is required for LDLR degradation. In light of these observations and the fact that PCSK9 in the circulation may cause the degradation of hepatic LDLR in the liver, PCSK9 would seem to be an attractive drug target for lowering LDL-c.
  • Application:
    ELISA
  • Components:
    • Microplate
    • 10X Wash Buffer
    • Dilution Buffer
    • Mouse PSCK9 Standard
    • HRP conjugated Detection Antibody
    • Substrate Reagent
    • Stop Solution
  • Description:

    The CycLex Research Product CircuLex Mouse/Rat PCSK9 ELISA Kit is used for the quantitative measurement of Mouse and Rat PCSK9 in serum, plasma, cell culture medium and other biological media. It can be used for 96 Assays.

  • Product Type:
    ELISA Kit
  • Research Area:
    Metabolism
  • Short Description:

    CircuLex Mouse/Rat PCSK9 ELISA Kit.

  • Size:
    96 Assays
Citations
  1. Carrier B et al. Alpha-lipoic acid reduces LDL-particle number and PCSK9 concentrations in high-fat fed obese Zucker rats. PLoS One. 9, e90863 (2014),
  2. Chen XW et al. SEC24A deficiency lowers plasma cholesterol through reduced PCSK9 secretion. Elife. 2, e00444 (2013),
  3. Galabova G et al. Peptide-based anti-PCSK9 vaccines - an approach for long-term LDLc management. PLoS One. 9, e114469 (2014),
  4. Sasaki M et al. Hepatic overexpression of idol increases circulating protein convertase subtilisin/kexin type 9 in mice and hamsters via dual mechanisms: sterol regulatory element-binding protein 2 and low-density lipoprotein receptor-dependent pathways. Arterioscler Thromb Vasc Biol. 34, 1171-8 (2014)
  5. (PLoS One 2012 Jul 27)
  6. An D et al. Identification of PCSK9 as a novel serum biomarker for the prenatal diagnosis of neural tube defects using iTRAQ quantitative proteomics. Sci Rep. 5, 17559 (2015)
  7. Berger JM et al. PCSK9-deficiency does not alter blood pressure and sodium balance in mouse models of hypertension. Atherosclerosis 239, 252-9 (2015)
  8. Butkinaree C et al. Amyloid Precursor-like Protein 2 and Sortilin Do Not Regulate the PCSK9 Convertase-mediated Low Density Lipoprotein Receptor Degradation but Interact with Each Other. J Biol Chem. 290, 18609-20 (2015)
  9. Haas ME et al. The Role of Proprotein Convertase Subtilisin/Kexin Type 9 in Nephrotic Syndrome-Associated Hypercholesterolemia. Circulation 134, 61-72 (2016)
  10. Lintner NG et al. Selective stalling of human translation through small-molecule engagement of the ribosome nascent chain. PLoS Biol. 15, e2001882 (2017)
  11. Sock ET et al. Combined Effects of Rosuvastatin and Exercise on Gene Expression of Key Molecules Involved in Cholesterol Metabolism in Ovariectomized Rats. PLoS One. 11, e0159550 (2016)
  12. Xu YX et al. Role of angiopoietin-like 3 (ANGPTL3) in regulating plasma level of low-density lipoprotein cholesterol. Atherosclerosis (2017) In press.
References
  1. Seidah NG, Benjannet S, Wickham L, Marcinkiewicz J, Jasmin SB, Stifani S, Basak A, Prat A, Chretien M (2003) Proc Natl Acad Sci USA 100:928–933.
  2. Abifadel M, Varret M, Rabes JP, Allard D, Ouguerram K, Devillers M, Cruaud C, Benjannet S, Wickham L, Erlich D, et al. (2003) Nat Genet 34:154–156.
  3. Leren TP (2004) Clin Genet 65:419–422.
  4. Allard D, Amsellem S, Abifadel M, Trillard M, Devillers M, Luc G, Krempf M, Reznik Y, Girardet JP, Fredenrich A, et al. (2005) Hum Mutat 26:497.
  5. Cohen JC, Boerwinkle E, Mosley TH, Jr, Hobbs HH (2006) N Engl J Med 354, 1264–1272.
  6. Berge KE, Ose L, Leren TP (2006) Arterioscler Thromb Vasc Biol 26:1094–1100.
  7. Maxwell KN, Breslow JL (2004) Proc Natl Acad Sci USA 101:7100–7105.
  8. Rashid S, Curtis DE, Garuti R, Anderson NN, Bashmakov Y, Ho YK, Hammer RE, Moon YA, Horton JD (2005) Proc Natl Acad Sci USA 102:5374–5379.
  9. Lagace, T. A., Curtis, D. E., Garuti, R., McNutt, M. C., Park, S. W., Prather, H. B., Anderson, N. N., Ho, Y. K., Hammer, R. E., and Horton, J. D. (2006) J. Clin. Investig. 116, 2995–3005
  10. Cameron, J., Holla, O. L., Ranheim, T., Kulseth, M. A., Berge, K. E., and Leren, T. P. (2006) Hum. Mol. Genet. 15, 1551–1558
  11. Zhang, D. W., Lagace, T. A., Garuti, R., Zhao, Z., McDonald, M., Horton, J. D., Cohen, J. C., and Hobbs, H. H. (2007) J. Biol. Chem. 282, 18602–18612