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C-reactive protein, pentraxin-related
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| CRP drawn from PDB 1B09 | ||
| Available structures: 1b09, 1gnh, 1lj7 | ||
| Identifiers | ||
| Symbol(s) | CRP; MGC149895; MGC88244; PTX1 | |
| External IDs | OMIM: 123260 MGI: 88512 HomoloGene: 476 | |
| RNA expression pattern | ||
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| Orthologs | ||
| Human | Mouse | |
| Entrez | 1401 | 12944 |
| Ensembl | ENSG00000132693 | ENSMUSG00000037942 |
| Uniprot | P02741 | Q542I3 |
| Refseq | NM_000567 (mRNA) NP_000558 (protein) |
NM_007768 (mRNA) NP_031794 (protein) |
| Location | Chr 1: 157.95 - 157.95 Mb | Chr 1: 174.53 - 174.54 Mb |
| Pubmed search | [3] | [4] |
C-reactive protein (CRP) is a protein produced as part of the inflammatory process. The Protein Data Bank ( PDB) is a repository for 3-D structural data of Proteins and Nucleic acids These data typically obtained by X-ray crystallography The Human Genome Organisation (HUGO is an organization involved in the Human Genome Project, a project about mapping the human genome The Mouse Genome Informatics (MGI website is run by The Jackson Laboratory. HomoloGene, a tool of the National Center for Biotechnology Information (NCBI is a system for automated detection of homologs (similarity attributable to descent The Entrez Global Query Cross-Database Search System is a powerful Federated search engine or Web portal that allows users to search many discrete Health sciences Ensembl is a joint scientific project between the European Bioinformatics Institute and the Wellcome Trust Sanger Institute, which was launched in 1999 in response to the imminent UniProt is the uni versal prot ein resource a central repository of Protein data created by combining Swiss-Prot, TrEMBL PubMed is a free search engine for accessing the MEDLINE database of citations and abstracts of biomedical research articles It is a routine test for heart failure; high levels of CRP may predict a bad outcome. (However, it is an unreliable test for heart failure, because inflammation from other causes also raises CRP. )
CRP is a plasma protein, an acute phase protein produced by the liver[1] and by adipocytes. Blood proteins, also called serum proteins, are Proteins found in Blood plasma. Acute-phase proteins are a class of Proteins whose plasma concentrations increase (positive acute phase proteins or decrease (negative acute phase proteins in response to The liver is a vital organ in the human body and is present in Vertebrates and some other animals [2] It is a member of the pentraxin family of proteins. The Pentraxins are a family of Proteins characterised by Calcium dependent Ligand binding and a distinctive flattened β-jellyroll structure similar to [1] It is not related to C-peptide or protein C. C-peptide is a Peptide which is made when Proinsulin is split into Insulin and C-peptide Protein C is a major physiological Anticoagulant. It is a Vitamin K -dependent Serine protease Enzyme ( that is activated by Thrombin
Contents |
History and nomenclature
C-reactive protein was originally discovered by Tillett and Francis in 1930 as a substance in the serum of patients with acute inflammation that reacted with the C polysaccharide of pneumococcus. Inflammation ( Latin, inflamatio, to set on fire is the complex biological response of vascular tissues to harmful stimuli such as Pathogens Streptococcus pneumoniae, or pneumococcus, is a Gram-positive, alpha-hemolytic diplococcus aerotolerant anaerobe and a member of the Genus [3] Initially it was thought that CRP might be a pathogenic secretion, as it was elevated in people with a variety of illnesses, including carcinomas. Discovery of hepatic synthesis and secretion of CRP closed that debate. It is thought to bind to phosphocholine, thus initiating recognition and phagocytosis of damaged cells. Phosphocholine (PC is an intermediate in the synthesis of Phosphatidylcholine in tissues Phagocytosis is the cellular process of engulfing solid particles by the Cell membrane to form an internal Phagosome, or "food vacuole [1]
Genetics and biochemistry
The CRP gene is located on the first chromosome (1q21-q23). A chromosome is an organized structure of DNA and Protein that is found in cells. CRP is a 224 residue protein[4] with a monomer molar mass of 25106 Da. The unified atomic mass unit ( u) or Dalton ( Da) or sometimes universal mass unit, is an unit of Mass used to express The protein is an annular pentameric disc in shape. Proteins with this type of configuration are known as pentraxins. The Pentraxins are a family of Proteins characterised by Calcium dependent Ligand binding and a distinctive flattened β-jellyroll structure similar to Native CRP is a bit different as it has 10-subunits making two pentameric discs, with an overall molecular mass of 251060 Da.
Function
CRP is a member of the class of acute phase reactants as its levels rise dramatically during inflammatory processes occurring in the body. Inflammation ( Latin, inflamatio, to set on fire is the complex biological response of vascular tissues to harmful stimuli such as Pathogens This increment is due to a rise in the plasma concentration of IL-6, which is produced predominantly by macrophages[1] as well as adipocytes. [2] CRP binds to phosphorylcholine on microbes. It is thought to assist in complement binding to foreign and damaged cells and enhances phagocytosis by macrophages, which express a receptor for CRP. The complement system is a Biochemical cascade that helps clear Pathogens from an organism It is also believed to play an important role in innate immunity, as an early defense system against infections.
CRP rises up to 50,000 fold in acute inflammation, such as infection. It rises above normal limits within 6 hours, and peaks at 48 hours. Its half-life is constant, and therefore its level is mainly determined by the rate of production (and hence the severity of the precipitating cause). Serum amyloid A is a related acute phase marker that responds rapidly in similar circumstances. Serum amyloid A (SAA proteins are a family of Apolipoproteins associated with High-density lipoprotein (HDL in plasma [1]
Diagnostic use
CRP is used mainly as a marker of inflammation. Apart from liver failure, there are few known factors that interfere with CRP production. Liver failure is the inability of the Liver to perform its normal synthetic and metabolic function as part of normal physiology [1]
Measuring and charting C-reactive protein values can prove useful in determining disease progress or the effectiveness of treatments. Blood, usually collected in a serum-separating tube, is analysed in a medical laboratory or at the point of testing. Blood is a specialized Bodily fluid that delivers necessary substances to the body's cells such as nutrients and oxygen—and transports Waste products Serum-separating tubes, also known as serum separator tubes or SSTs are used in Medical Clinical chemistry tests requiring Blood serum. A medical laboratory or clinical laboratory is a Laboratory where tests are done on clinical specimens in order to get information about the Health
Various analytical methods are available for CRP determination, such as ELISA, immunoturbidimetry, rapid immunodiffusion and visual agglutination. Enzyme-Linked ImmunoSorbent Assay, also called ELISA, Enzyme ImmunoAssay or EIA, is a biochemical technique used mainly in Immunology Immunodiffusion is a diagnostic test which involves diffusion through a substance such as Agar. Agglutination is the clumping of particles The word agglutination comes from the Latin agglutinare, meaning "to glue to
Viral infections tend to give a lower CRP level than bacterial infection.
Cardiology diagnostic test
Arterial damage is thought to result from inflammation due to chemical insults. CRP is a general marker for inflammation and infection, so it can be used as a very rough proxy for heart disease risk. Since many things can cause elevated CRP, this is not a very specific prognostic indicator. See also Specificity Specific can mean Particular In science specific can denote that a measurement is expressed [5] Nevertheless, a level above 2. 4 mg/l has been associated with a doubled risk of a coronary event compared to levels below 1 mg/l. [1]
Glycosylation
CRP may have sugars—sialic acid, glucose, galactose and mannose—attached to it (i. Sialic acid is a generic term for the N - or O -substituted derivatives of Neuraminic acid, a Monosaccharide with a nine- Carbon backbone Glucose (Glc a Monosaccharide (or simple Sugar) also known as grape sugar, is an important Carbohydrate in Biology. Galactose (Gal (also called brain sugar) is a type of Sugar which is less sweet than Glucose. Mannose is a Sugar Monomer of the Hexose series of Carbohydrates Metabolism Mannose enters the carbohydrate Metabolism e. it gets glycosylated. Glycosylation is the enzymatic process that links Saccharides to produce glycans, either free or attached to Proteins and Lipids This enzymatic ) In different disease states, one or two amino-acids get lopped off CRP. It retains its activity, but these losses open it up to glycosylation. Different diseases (each of which raise CRP) will add sugars to it in different patterns. The patterns are different across diseases, but similar amongst patients who had the same disease. A 2003 study looked at patients with lupus, leukemia, tuberculosis, leishmaniasis, Cushing's syndrome and bone cancer. (Healthy subjects did not have enough CRP to successfully characterize "normal" CRP. )
Previous work had shown that CRP increased the rate at which a particular parasite could invade blood cells. Trypanosomes are a group of Kinetoplastid protozoa distinguished by having only a single Flagellum. The study showed that the different CRPs had very different potencies in this regard. The authors speculate that subtyping CRP may give us more insight into heart attack mechanisms. Although this did not demonstrate whether this glycation of CRP was a 'good thing' or a 'bad thing', it offered circumstantial evidence that the differing glycation is part of CRPs mode-of-action. [6]
Role in cardiovascular disease
Recent research suggests that patients with elevated basal levels of CRP are at an increased risk for diabetes,[7][8] hypertension and cardiovascular disease. Diabetes mellitus (ˌdaɪəˈbiːtiːz or /ˌdaɪəˈbiːtəs/ /məˈlaɪtəs/ or /ˈmɛlətəs/ often referred to simply as diabetes ( Ancient Greek: grc Hypertension, also referred to as high blood pressure, HTN or HPN, is a medical condition in which the Blood pressure is chronically elevated Cardiovascular disease or cardiovascular diseases refers to the class of diseases that involve the Heart or Blood vessels ( arteries and A study of over 700 nurses showed that those in the highest quartile of trans fat consumption had blood levels of C-reactive protein (CRP, a pro-inflammatory cytokine which is a cardiovascular disease risk factor) that were 73% higher than those in the lowest quartile. In Descriptive statistics, a quartile is any of the three values which divide the sorted Data set into four equal parts so that each part represents one fourth of Cytokines are a category of signalling Proteins and Glycoproteins that like Hormones and Neurotransmitters, are used extensively in cellular Cardiovascular disease or cardiovascular diseases refers to the class of diseases that involve the Heart or Blood vessels ( arteries and [9] Although one group of researchers indicated that CRP may only be a moderate risk factor for cardiovascular disease,[10] this study (known as the Reykjavik Study) was found to have some problems for this type of analysis related to the characteristics of the population studied, and there was an extremely long follow-up time which may have attenuated the association between CRP and future outcomes. [11] Others have shown that CRP can exacerbate ischemic necrosis in a complement-dependent fashion and that CRP inhibition can be a safe and effective therapy for myocardial and cerebral infarcts; so far, this has only been demonstrated in animal models. In Medicine, ischemia ( Greek ισχαιμία, isch- is restriction hema or haema is Blood) is a restriction Necrosis (in Greek Νεκρός = "dead" is the name given to unnatural Death of cells and living tissue. The complement system is a Biochemical cascade that helps clear Pathogens from an organism Myocardium is the muscular tissue of the Heart. Relationship to other layers The other tissues of the heart are the Endocardium In Medicine, an infarction is the process resulting in a Macroscopic area of necrotic tissue in some organ caused by loss of adequate Blood supply [12]
To measure the CRP level, a "high-sensitivity" CRP or hs-CRP test needs to be performed and analyzed by a laboratory. This is an automated blood test designed for greater accuracy in measuring low levels of CRP, which allows the physician to assess cardiovascular risk. If a result in the low-risk range is found ( < 1 mg/L), it does not need repeating. Higher levels need repeating, and clinical evaluation as necessary.
Role in cancer
The role of inflammation in cancer is not well known. Some organs of the body show greater risk of cancer when they are chronically inflamed.
Blood samples of persons with colon cancer have an average CRP concentration of 2. Colorectal cancer, also called colon cancer or large bowel cancer, includes Cancerous growths in the colon, Rectum and 69 milligrams per liter. Persons without colon cancer average 1. 97 milligrams per liter. The difference was statistically significant. [13] These findings concur with previous studies that indicate that anti-inflammatory drugs could lower colon cancer risk. Non-steroidal anti-inflammatory drugs, usually abbreviated to NSAID s or NAID s, are drugs with Analgesic, Antipyretic and in higher [14]
See also
Additional images
 C-reactive protein |
References
- ^ a b c d e f g Pepys MB, Hirschfield GM (2003). The Acute phase of an injury is the period of time in between when the injury is sustained and the beginning of the Sub-acute phase. The erythrocyte sedimentation rate (ESR also called a sedimentation rate, sed rate, or Biernacki Reaction, is the rate at which Red blood cells Immunology is a broad branch of biomedical Science that covers the study of all aspects of the Immune system in all Organisms It deals with "C-reactive protein: a critical update". J. Clin. Invest. 111 (12): 1805-12. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 12813013. Full text at PMC: 161431
- ^ a b Lau DC, Dhillon B, Yan H, Szmitko PE, Verma S (2005). PubMed Central is a free digital database of full-text Scientific literature in biomedical and life sciences "Adipokines: molecular links between obesity and atheroslcerosis". Am. J. Physiol. Heart Circ. Physiol. 288 (5): H2031–41. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 15653761.
- ^ Tillett WS, Francis Jr T (1930). "Serological reactions in pneumonia with a nonprotein somatic fraction of pneumococcus" (PDF). J Exp Med 52: 561-585. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document.
- ^ NCBI Entrez Protein #CAA39671 [1]
- ^ Lloyd-Jones DM, Liu K, Tian L, Greenland P (2006). "Narrative Review: Assessment of C-Reactive Protein in Risk Prediction for Cardiovascular Disease". Ann Intern Med 145 (1): 35-42. PMID 16818927.
- ^ Tanusree DAS et al. "Induction of glycosylation in human C-reactive protein under different pathological conditions" (pdf). Biochem. J. (2003) 373, 345–355.
- ^ Pradhan AD (2001). "C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus". JAMA 286: 327–334. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 11466099.
- ^ Dehghan A (2007). "Genetic variation, C-reactive protein levels, and incidence of diabetes. ". Diabetes 56: 872. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 17327459.
- ^ Esther Lopez-Garcia (2005). "Consumption of Trans Fatty Acids Is Related to Plasma Biomarkers of Inflammation and Endothelial Dysfunction". The Journal of Nutrition 135 (3): 562–566. PMID 15735094.
- ^ John Danesh (2004). "C-Reactive Protein and Other Circulating Markers of Inflammation in the Prediction of Coronary Heart Disease". New England Journal of Medicine 350 (14): 1387–1397. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 15070788.
- ^ Koenig, Wolfgang (2006). C-Reactive Protein – A Critical Cardiovascular Risk Marker [2]
- ^ Pepys MB, Hirschfield GM, Tennent GA, Gallimore JR, Kahan MC, Bellotti V, Hawkins PN, Myers RM, Smith MD, Polara A, Cobb AJ, Ley SV, Aquilina JA, Robinson CV, Sharif I, Gray GA, Sabin CA, Jenvey MC, Kolstoe SE, Thompson D, Wood SP (2006). "Targeting C-reactive protein for the treatment of cardiovascular disease. ". Nature 440: 1217–1221. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 16642000.
- ^ Erlinger TP, Platz EA, Rifai N, Helzlsouer KJ (2004). "C-reactive protein and the risk of incident colorectal cancer". Journal of the American Medical Association 291 (Feb. 4): 585-590. PMID 14762037.
- ^ Baron JA, et al (2003). "A randomized trial of aspirin to prevent colorectal adenomas". New England Journal of Medicine 348: 891-899. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 12621133.
External links
- MedlinePlus Encyclopedia 003356
- Inflammation, Heart Disease and Stroke: The Role of C-Reactive Protein (American Heart Association)
- MeSH C-Reactive+Protein
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