Dihydroxy-E,Z,E-PUFA
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Dihydroxy-E,Z,E-PUFA
Dihydroxy-''E'',''Z'',''E''-PUFA are metabolites of polyunsaturated fatty acids (PUFA) that possess two hydroxyl residues and three in series conjugated double bonds having the ''E'',''Z'',''E'' cis-trans configuration. These recently classified metabolites are distinguished from the many other dihydroxy-PUFA with three conjugated double bonds that do not have this critical ''E'',''Z'',''E'' configuration: they inhibit the function of platelets and therefore may be involved in controlling and prove useful for inhibiting human diseases which involve the pathological activation of these blood-borne elements. Biochemistry Dihydroxy-''E'',''Z'',''E''-PUFA are metabolites of a) docosahexaenoic acid (DHA, i.e. 4''Z'',7''Z'',10''Z'',13''Z'',16''Z'',19''Z''-docosahexaenoic acid), b) α-Linolenic acid (ALA, i.e. ''9''Z,12''Z'',15''Z''-octadecatrienoic acid), an c) arachidonic acid (AA); ''E'',''Z'',''E''-DHA and ''E'',''Z'',''E'' AA metabolites are termed poxytrins; ALA metabolites ar ...
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Specialized Proresolving Mediators
Specialized pro-resolving mediators (SPM, also termed specialized proresolving mediators) are a large and growing class of cell signaling molecules formed in cells by the metabolism of polyunsaturated fatty acids (PUFA) by one or a combination of lipoxygenase, cyclooxygenase, and cytochrome P450 monooxygenase enzymes. Pre-clinical studies, primarily in animal models and human tissues, implicate SPM in orchestrating the resolution of inflammation. Prominent members include the resolvins and Protectin D1, protectins. SPM join the long list of other physiological agents which tend to limit inflammation (see ) including glucocorticoids, interleukin 10 (an anti-inflammatory cytokine), interleukin 1 receptor antagonist (an inhibitor of the action of pro-inflammatory cytokine, interleukin 1), annexin A1 (an inhibitor of formation of pro-inflammatory metabolites of polyunsaturated fatty acids), and the gaseous resolvins, carbon monoxide (see ), nitric oxide (see ), and hydrogen sulfide (se ...
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Polyunsaturated Fatty Acids
Polyunsaturated fatty acids (PUFAs) are fatty acids that contain more than one double bond in their backbone. This class includes many important compounds, such as essential fatty acids and those that give drying oils their characteristic property. Polyunsaturated fatty acids can be classified in various groups by their chemical structure: * methylene-interrupted polyenes * conjugated fatty acids * other PUFAs Based on the length of their carbon backbone, they are sometimes classified in two groups: * short chain polyunsaturated fatty acids (SC-PUFA), with 18 carbon atoms * long-chain polyunsaturated fatty acids (LC-PUFA) with 20 or more carbon atoms Dietary sources Types Methylene-interrupted polyenes These fatty acids have 2 or more ''cis'' double bonds that are separated from each other by a single methylene bridge (--). This form is also sometimes called a ''divinylmethane pattern''. The essential fatty acids are all omega-3 and -6 methylene-interrupted fatty ac ...
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Thromboxane A2
Thromboxane A2 (TXA2) is a type of thromboxane that is produced by activated platelets during hemostasis and has prothrombotic properties: it stimulates activation of new platelets as well as increases platelet aggregation. This is achieved by activating the thromboxane receptor, which results in platelet-shape change, inside-out activation of integrins, and degranulation. Circulating fibrinogen binds these receptors on adjacent platelets, further strengthening the clot. Thromboxane A2 is also a known vasoconstrictor and is especially important during tissue injury and inflammation. It is also regarded as responsible for Prinzmetal's angina. Receptors that mediate TXA2 actions are thromboxane A2 receptors. The human TXA2 receptor (TP) is a typical G protein-coupled receptor (GPCR) with seven transmembrane segments. In humans, two TP receptor splice variants – TPα and TPβ – have so far been cloned. Synthesis and breakdown TXA2 is generated from prostaglandin H2 by thromboxa ...
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Cell Signaling
In biology, cell signaling (cell signalling in British English) or cell communication is the ability of a cell to receive, process, and transmit signals with its environment and with itself. Cell signaling is a fundamental property of all cellular life in prokaryotes and eukaryotes. Signals that originate from outside a cell (or extracellular signals) can be physical agents like mechanical pressure, voltage, temperature, light, or chemical signals (e.g., small molecules, peptides, or gas). Cell signaling can occur over short or long distances, and as a result can be classified as autocrine, juxtacrine, intracrine, paracrine, or endocrine. Signaling molecules can be synthesized from various biosynthetic pathways and released through passive or active transports, or even from cell damage. Receptors play a key role in cell signaling as they are able to detect chemical signals or physical stimuli. Receptors are generally proteins located on the cell surface or within the interio ...
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Cell Communication
In biology, cell signaling (cell signalling in British English) or cell communication is the ability of a Cell (biology), cell to receive, process, and transmit signals with its environment and with itself. Cell signaling is a fundamental property of all Cell (biology), cellular life in prokaryotes and eukaryotes. Signals that originate from outside a cell (or extracellular signals) can be physical agents like mechanical pressure, membrane potential , voltage, temperature, light, or chemical signals (e.g., small molecules, peptides, or gas). Cell signaling can occur over short or long distances, and as a result can be classified as autocrine, juxtacrine, intracrine, paracrine, or endocrine. Signaling molecules can be synthesized from various biosynthetic pathways and released through passive transport , passive or active transports, or even from cell damage. Receptor (biochemistry), Receptors play a key role in cell signaling as they are able to detect chemical signals or physic ...
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Cell Biology
Cell biology (also cellular biology or cytology) is a branch of biology that studies the structure, function, and behavior of cells. All living organisms are made of cells. A cell is the basic unit of life that is responsible for the living and functioning of organisms. Cell biology is the study of structural and functional units of cells. Cell biology encompasses both prokaryotic and eukaryotic cells and has many subtopics which may include the study of cell metabolism, cell communication, cell cycle, biochemistry, and cell composition. The study of cells is performed using several microscopy techniques, cell culture, and cell fractionation. These have allowed for and are currently being used for discoveries and research pertaining to how cells function, ultimately giving insight into understanding larger organisms. Knowing the components of cells and how cells work is fundamental to all biological sciences while also being essential for research in biomedical fields such as ...
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Maresin
Maresin 1 (MaR1 or 7''R'',14''S''-dihydroxy-4''Z'',8''E'',10''E'',12''Z'',16''Z'',19''Z''-docosahexaenoic acid) is a macrophage-derived mediator of inflammation resolution coined from macrophage mediator in resolving inflammation. Maresin 1, and more recently defined maresins, are 12-lipoxygenase-derived metabolites of the omega-3 fatty acid, docosahexaenoic acid (DHA), that possess potent anti-inflammatory, pro-resolving, protective, and pro-healing properties similar to a variety of other members of the specialized proresolving mediators (SPM) class of polyunsaturated fatty acid (PUFA) metabolites. SPM are dihydroxy, trihydroxy, and epoxy-hydroxy metabolites of long chain PUFA made by certain dioxygenase enzymes viz., cyclooxygenases and lipoxygenases. In addition to the maresins, this class of mediators includes: the 15-lipoxygenase (i.e. ALOX15 and/or possibly ALOX15B)-derived Lipoxin A4 and B4 metabolites of the omega 6 fatty acid, arachidonic acid; the cyclooxygenase 2- ...
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Eicosanoid
Eicosanoids are signaling molecules made by the enzymatic or non-enzymatic oxidation of arachidonic acid or other polyunsaturated fatty acids (PUFAs) that are, similar to arachidonic acid, around 20 carbon units in length. Eicosanoids are a sub-category of oxylipins, i.e. oxidized fatty acids of diverse carbon units in length, and are distinguished from other oxylipins by their overwhelming importance as cell signaling molecules. Eicosanoids function in diverse physiological systems and pathological processes such as: mounting or inhibiting inflammation, allergy, fever and other immune responses; regulating the abortion of pregnancy and normal childbirth; contributing to the perception of pain; regulating cell growth; controlling blood pressure; and modulating the regional flow of blood to tissues. In performing these roles, eicosanoids most often act as autocrine signaling agents to impact their cells of origin or as paracrine signaling agents to impact cells in the proximity of ...
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Thromboxane Receptor
The thromboxane receptor (TP) also known as the prostanoid TP receptor is a protein that in humans is encoded by the ''TBXA2R'' gene, The thromboxane receptor is one among the five classes of prostanoid receptors and was the first eicosanoid receptor cloned. The TP receptor derives its name from its preferred endogenous ligand thromboxane A2. Gene The gene responsible for directing the synthesis of the thromboxane receptor, ''TBXA2R'', is located on chromosome 19 at position p13.3, spans 15 kilobases, and contains 5 exons. ''TBXA2R'' codes for a member of the G protein-coupled super family of seven-transmembrane receptors. Heterogeneity Molecular biology findings have provided definitive evidence for two human TP receptor subtypes. The originally cloned TP from placenta (343 amino acids in length) is known as the α isoform and the splice variant cloned from endothelium (with 407 amino acids), termed the β isoform. The first 328 amino acids are the same for both isoforms, ...
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COX-1
Cyclooxygenase 1 (COX-1), also known as prostaglandin G/H synthase 1, prostaglandin-endoperoxide synthase 1 or prostaglandin H2 synthase 1, is an enzyme that in humans is encoded by the ''PTGS1'' gene. In humans it is one of two cyclooxygenases. History Cyclooxygenase (COX) is the central enzyme in the biosynthetic pathway to prostaglandins from arachidonic acid. This protein was isolated more than 40 years ago and cloned in 1988. Gene and isozymes There are two isozymes of COX encoded by distinct gene products: a constitutive COX-1 (this enzyme) and an inducible COX-2, which differ in their regulation of expression and tissue distribution. The expression of these two transcripts is differentially regulated by relevant cytokines and growth factors. This gene encodes COX-1, which regulates angiogenesis in endothelial cells. COX-1 is also involved in cell signaling and maintaining tissue homeostasis. A splice variant of COX-1 termed COX-3 was identified in the central nervous sy ...
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Nanomolar
Molar concentration (also called molarity, amount concentration or substance concentration) is a measure of the concentration of a chemical species, in particular of a solute in a solution, in terms of amount of substance per unit volume of solution. In chemistry, the most commonly used unit for molarity is the number of moles per liter, having the unit symbol mol/L or mol/ dm3 in SI unit. A solution with a concentration of 1 mol/L is said to be 1 molar, commonly designated as 1 M. Definition Molar concentration or molarity is most commonly expressed in units of moles of solute per litre of solution. For use in broader applications, it is defined as amount of substance of solute per unit volume of solution, or per unit volume available to the species, represented by lowercase c: :c = \frac = \frac = \frac. Here, n is the amount of the solute in moles, N is the number of constituent particles present in volume V (in litres) of the solution, and N_\text is the Avo ...
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