Human Proprotein Convertase 9/PCSK9 Quantikine ELISA Kit Summary
Background |
The Quantikine Human PCSK9 immunoassay is a 4.5 hour solid phase ELISA designed to measure PCSK9 in cell culture supernates, cell lysates, serum, and plasma. It contains NS0-expressed recombinant human PCSK9 and has been shown to accurately quantitate the recombinant factor. Results obtained using natural PCSK9 showed linear curves that were parallel to the standard curves obtained using the... Quantikine kit standards. These results indicate that this kit can be used to determine relative mass values for naturally occurring PCSK9. |
Specificity |
Natural and recombinant human PCSK9. This assay recognizes free and LDLR-bound PCSK9. |
Source |
N/A |
Assay Type |
Solid Phase Sandwich ELISA |
Inter-Assay |
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Intra-Assay |
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Spike Recovery |
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Sample Volume |
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Gene |
PCSK9 |
Applications/Dilutions
Dilutions |
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Application Notes |
No significant interference observed with available related molecules. |
Publications |
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Packaging, Storage & Formulations
Storage |
Store the unopened product at 2 - 8 °C. Do not use past expiration date. |
Notes
This product is produced by and ships from R&D Systems, Inc., a Bio-Techne brand.
Alternate Names for Human Proprotein Convertase 9/PCSK9 Quantikine ELISA Kit
Background
Proprotein convertase subtilisin kexin 9 (PCSK9), also named neural apoptosis-regulated
convertase 1 (NARC-1), is a member of the proteinase K subfamily of subtilisin-related serine
endoproteases. The full-length protein has 692 amino acids, including a signal peptide, a
pro- domain, and a catalytic domain. PCSK9 is highly expressed in the liver, intestine, and
kidney. It is initially synthesized as a soluble 74 kDa precursor protein. In the endoplasmic
reticulum, it undergoes autocatalytic intramolecular cleavage to generate a 14 kDa
pro- domain and a 60 kDa catalytic domain. These two domains remain associated when PCSK9
is secreted outside the cells (1-3). The primary physiologic function of PCSK9 is to mediate the
degradation of low density lipoprotein receptor (LDL R). Early observations indicated that
gain-of-function missense mutations in the PCSK9 gene can cause an autosomal dominant
form of hypercholesterolemia (4, 5). The expression of PCSK9 was observed to be up-regulated
by the sterol regulatory element binding proteins (SREBPs), a family of transcription factors
that are responsible for the upregulation of genes involved in cholesterol and fatty acid
metabolism, such as the LDL R gene (6, 7). Further experimental evidence revealed that in mice,
when the PCSK9 gene was knocked out, the number of LDL R in hepatocytes increased,
whereas when PCSK9 was over-expressed, the amount of LDL R protein was reduced in the
liver (8, 9). In humans, genetic analyses have shown that individuals who have nonsense or
loss-of-function mutations in the PCSK9 gene have significantly lower plasma LDL cholesterol
levels (10, 11). These investigations clearly indicated that PCSK9 plays a key role in reducing the
hepatic LDL R levels. Recently, the underlying mechanism has been uncovered: under normal
physiologic conditions, the LDL R is internalized on the cell surface and directed to the
endosomes in order to be recycled back to the cell surface. PCSK9 binds to the EGF domain of
the LDL R and prevents LDL R from being sorted to the endosomes. Instead, the PCSK9/LDL R
complex is redistributed to the lysosomes for degradation (12-14). As such, PCSK9 regulates the
amount of LDL R in the circulation and modulates cholesterol levels. Serum PCSK9
concentrations have been found to be directly associated with cholesterol levels (15, 16). Since
individuals with loss-of-function PCSK9 mutations have strikingly reduced risk of coronary
heart diseases, PCSK9 has become an attractive drug target in recent years (17, 18). One
approach is to generate small molecules that are able to interfere with PCSK9 autoactivation
and its interaction with LDL R. Other approaches aiming to reduce the amounts of PCSK9 in the
circulation, such as small interfering RNAs (siRNAs), have also shown promise (19, 20).
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⚠ WARNING: This product can expose you to chemicals including N,N-Dimethylforamide, which is known to the State of California to cause cancer. For more information, go to www.P65Warnings.ca.gov.
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