alpha-1 acid glycoprotein

Alpha-1-acid glycoprotein (AGP) or orosomucoid (ORM) is an acute phase protein synthesized in response to pro-inflammatory cytokines early in the inflammatory response.

AGP gene expression is controlled by a combination of the major regulatory mediators – glucocorticoids and a cytokine network involving IL-1β, TNF-α, IL-6, and IL-6 related cytokines. Human AGP is a 41-43 kDa glycoprotein with single chain of 183 amino acids plus five to six highly sialylated complex-type-N-linked glycans, rendering the molecule heavily glycosylated (45%). Binding affinity and immunomodulatory activities of AGP are mostly dependent on carbohydrate composition.

Alpha-1-acid glycoprotein. Fournier T, Medjoubi-N N, Porquet D. Biochim Biophys Acta. 2000 Oct 18;1482(1-2):157-71.

tags [Proteins] [acute phase] [alpha-1-acid glycoprotein] [inflammation] [cytokine]

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alpha 1-antichymotrypsin

alpha 1-Antichymotrypsin (ACT) is an an acute phase protein synthesized in response to pro-inflammatory cytokines early in the inflammatory response.

ACT is a member of the serine proteinase inhibitor (serpin) family that inhibits neutrophilic proteinases – chymotrypsin, cathepsin G, chymases from mast cells, and elastase – protecting tissue from damage by these proteolytic enzymes. ACT is a glycoprotein found in alpha(1)-globulin region in human serum. Alpha 1-antichymotrypsin contains a reactive centre loop that interacts with cognate proteinases, resulting in loop cleavage and a major conformational change.

As an acute phase protein, ACT is active in the control of immune and inflammatory responses, and acts as a tumor marker. ACT inhibits CTL-mediated lysis (CML).

ACT has been identified as a major constituent of the neurofibrillary plaques associated with Alzheimers disease, where it probably enhances the rate of amyloid-fibril formation. Genetic data also suggests that alpha 1-antichymotrypsin is important in the pathogenesis of Alzheimer's disease.[s]

tags [Proteins] [alpha-1 antichymotrypsin] [inflammation] [cytokine] [serine protease inhibitor] [Alzheimers]

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alpha 1-antitrypsin

Alpha 1-antitrypsin or α1-antitrypsin (A1AT) or alpha-1 proteinase inhibitor (α1-PI) is an an acute phase protein synthesized in response to pro-inflammatory cytokines early in the inflammatory response.

A1AT is a 52 kDa prototypical serine protease inhibitor (serpin) that protects against enzymes released by inflammatory cells, particularly elastase, which is released from neutrophilic granules. A1AT forms covalent bonds with both elastase and trypsin, irreversibly inactivating these proteolytic enzymes.

Alpha 1-antitrypsin deficiency is a hereditary disorder in which inability to inactivate elastase and trypsin allows inflammatory tissue breakdown, causing pulmonary emphysema and hepatic cirrhosis in severe cases.

tags [Proteins] [alpha 1-antitrypsin] [inflammation] [cytokine] [serine protease inhibitor]

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alpha 2-macroglobulin

Alpha-2 macroglobulin (A2M), α-2 macroglobulin is an an acute phase protein synthesized in response to pro-inflammatory cytokines early in the inflammatory response.

A2M is a large plasma protein produced by the liver, and is a major component of the alpha-2 band in protein electrophoresis. A2M interacts and captures virtually any proteinase whether self or foreign, suggesting a function as a unique "panproteinase inhibitor." A2M also removes the active forms of the gelatinase (MMP-2 and MMP-9) from the circulation, binding to scavenger receptors on the phagocytes. In the mechanism termed "clearance of activated alpha 2-macroglobulin", ACT undergoes Ca(2+)-dependent binding to a member of the low-density lipoprotein receptor supergene family that mediates cellular uptake by endocytosis and delivery to endosomes and lysosomes. Thus, the peptide binding function of A2M allows targeting of biologically active peptides to different cell types expressing the A2M receptor. Complexes internalized through this binding may be dispatched into different pathways of endocytic/lysosomal pathways in a cell type-specific manner.[r]

A2M ratios are increased in nephrotic syndrome when the kidneys lose smaller plasma proteins (proteinuria). A common variant of α2-macroglobulin is associated with increased risk of Alzheimers disease.

 Scavenger Receptors

tags [Proteins] [alpha 2- macroglobulin] [inflammation] [cytokine] [serine protease inhibitor] [Alzheimers] [nephrotic+syndrome]

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coagulation factors

Coagulation factors participate in the coagulation cascade, which is initiated within 20 seconds of an injury to the endothelial cells that line blood vessels (primary hemostasis, acute phase reaction).

Coagulation factors are synthesized by the liver and their production increases in response to pro-inflammatory cytokines released in the acute phase early in the inflammatory response, in particular:
● factor VIII
● fibrinogen
● plasminogen
● prothrombin
● von Willebrand factor

tags [Proteins] [acute phase] [coagulation factors] [clotting cascade] [cytokine] [hemostasis]

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ferritin

Ferritin is an an acute phase protein synthesized in response to pro-inflammatory cytokines early in the inflammatory response.

Ferritin is the chief iron storage protein for both eukaryotes and prokaryotes, and is termed apoferritin when not combined with Fe(3+) ions. The globular ferritin protein complex comprises 24 subunits – hetero-oligomers of light (L) and heavy (H) chains encoded by homologous genes (vertebrates), H chains only in bacteria and plants. Free Fe is toxic, so cells employ ferritin molecules or aggregates (hemosiderin) to form protective Fe-protein complexes. Each ferritin molecule complexes around 4500 (Fe3+)ions.

Ferritin is found in most tissues, particularly in the bone marrow and reticuloendothelial system (or mononuclear phagocytic system). Serum ferritin levels are proportional to iron storage levels in humans and are employed as a part of the work-up for anemia, particurlarly iron-deficiency anemia. However, ferritin levels are increased by acute inflammation, hemochromatosis, malignancy, hyperthyroidism, Still's Disease, or hepatic disease (necrotic hepatocytes), so ferritin levels may be misleading when anemia is concomitant with these conditions.

tags [Proteins] [acute phase] [ferritin] [iron storage] [iron deficiency anemia] [inflammation] [hemochromatosis]

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haptoglobins

Haptoglobins (Hp) are acute phase proteins synthesized in response to pro-inflammatory cytokines early in the inflammatory response.

Haptoglobins are alpha-2-globulins that remove free hemoglobin from plasma by forming a stable complex that aids in recycling of heme iron.

Haptoglobins are elevated in inflammation, malignancies (particularly with metastases to bone), trauma, surgery, steroid or androgen therapy, and diabetes.

tags [Proteins] [acute phase] [haptoglobins] [alpha-2-globulins] [inflammation] [cytokine]

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NF-κB

NF-κB, Nuclear Factor kappa Bs, are ubiquitous transcription factors involved in responses to cellular stressors such as cytokines, free radicals, UV irradiation, bacterial antigens, and viral antigens.

▼ action of IκB : actions of NF-κB : family : free NF-κB : IκB : IkappaBalpha : IκB kinase : IKK : NF-κB family : NF-κB/rel : tumors and NF-κB : v-Rel ▼

Members of the NF-κB family are classified as NF-κB/Rel proteins because they display structural homology to the retroviral oncoprotein v-Rel, and include mammalian members:
● N-terminal homology with v-Rel
___ ● NF-κB1 (p50)
___ ● NF-κB2 (p52)
_ ● plus trans-activation domain in C-termini
____ ● RelA (p65)
____ ● RelB
____ ● c-Rel

[] 3D transcription factor NFkappaB -helix-loop-helix []

NF-κB1 and NF-κB2 are synthesized as large precursors (p105, and p100) that undergo selective degradation of their C-terminal region by the ubiquitin/proteasome pathway to generate the mature NF-κB subunits ( p50, and p52 respectively). Degradation of p100 to p52 is tightly regulated process, whereas p50 is generated by constitutive processing of p105. RelA, RelB, and c-Rel contain trans-activation domains at their C-termini. (p52 is not to be confused with the tumor suppressor gene p53.)

Inhibitor of kappa B (IκB, IkappaBalpha) inactivates NF-κB by sequestering NF-κB dimers within the cytoplasm. Activation of IκB kinase (IKK) by stress signals stimulates phosphorylation of two serine residues in IκB's regulatory domain, targetting the IκB molecules for ubiquitin/proteasome degradation, and releasing NF-κB from inhibition.

Free NF-κB translocates to the nucleus where it binds to specific κB sequences in DNA, initiating transcription of related genes, including those for immunoreceptors, cytokines, and its own inhibitor, IκB. Physiological activities mediated by NF-κB include cellular proliferation, and inflammatory, immune, and cellular survival responses. [] signaling pathways []

Many tumor types have chronically active, dysregulated NF-κB, resulting from:
● mutations in genes encoding the NF-κB transcription factors themselves, or
● mutations in genes that control NF-κB activity

tags [Proteins] [NFkB] [transcription+factors] [cytokines] [inflammation] [immune response]

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