Sphingosine-1-phosphate Receptor
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Sphingosine-1-phosphate Receptor
The sphingosine-1-phosphate receptors are a class of G protein-coupled receptors that are targets of the lipid signalling molecule Sphingosine-1-phosphate (S1P). They are divided into five subtypes: S1PR1, S1PR2, S1PR3, S1PR4 and S1PR5. Discovery In 1990, S1PR1 was the first member of the S1P receptor family to be cloned from endothelial cells. Later, S1PR2 and S1PR3 were cloned from rat brain and a human genomic library respectively. Finally, S1P4 and S1PR5 were cloned from in vitro differentiated human dendritic cells and rat cDNA library. Function The sphingosine-1-phosphate receptors regulate fundamental biological processes such as cell proliferation, angiogenesis, migration, cytoskeleton organization, endothelial cell chemotaxis, immune cell trafficking and mitogenesis. Sphingosine-1-phosphate receptors are also involved in immune-modulation and directly involved in suppression of innate immune responses from T cells. Subtypes Sphingosine-1-phosphate (S1P) receptors ar ...
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G Protein-coupled Receptors
G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily-related proteins that are cell surface receptors that detect molecules outside the cell and activate cellular responses. Coupling with G proteins, they are called seven-transmembrane receptors because they pass through the cell membrane seven times. Text was copied from this source, which is available under Attribution 2.5 Generic (CC BY 2.5) license. Ligands can bind either to extracellular N-terminus and loops (e.g. glutamate receptors) or to the binding site within transmembrane helices (Rhodopsin-like family). They are all activated by agonists although a spontaneous auto-activation of an empty receptor can also be observed. G protein-coupled receptors are found only in eukaryotes, including yeast, choanoflagellates, and a ...
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Mitogenesis
A mitogen is a small bioactive protein or peptide that induces a cell to begin cell division, or enhances the rate of division (mitosis). Mitogenesis is the induction (triggering) of mitosis, typically via a mitogen. The mechanism of action of a mitogen is that it triggers signal transduction pathways involving mitogen-activated protein kinase (MAPK), leading to mitosis. The cell cycle Mitogens act primarily by influencing a set of proteins which are involved in the restriction of progression through the cell cycle. The G1 checkpoint is controlled most directly by mitogens: further cell cycle progression does not need mitogens to continue. The point where mitogens are no longer needed to move the cell cycle forward is called the "restriction point" and depends on cyclins to be passed.Bohmer et al. "Cytoskeletal Integrity Is Required throughout the Mitogen Stimulation Phase of the Cell Cycle and Mediates the Anchorage-dependent Expression of Cyclin DI". January 1996, Molecular ...
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Ozanimod
Ozanimod, sold under the brand name Zeposia, is an immunomodulatory medication for the treatment of relapsing multiple sclerosis and ulcerative colitis. It acts as a sphingosine-1-phosphate (S1P) receptor agonist, sequestering lymphocytes to peripheral lymphoid organs and away from their sites of chronic inflammation. The most common adverse reactions are upper respiratory infection, hepatic transaminase elevation, orthostatic hypotension, urinary tract infection, back pain, and hypertension. Ozanimod was approved for medical use in the United States in March 2020, in the European Union in May 2020, and in Australia in July 2020. Medical uses In the United States, ozanimod is indicated for the treatment of adults with relapsing forms of multiple sclerosis, to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease; and with moderately to severely active ulcerative colitis. In the European Union and in Australia, ozanimod ...
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Fingolimod
Fingolimod, sold under the brand name Gilenya, is an immunomodulating medication, mostly used for treating multiple sclerosis (MS). Fingolimod is a sphingosine-1-phosphate receptor modulator, which sequesters lymphocytes in lymph nodes, preventing them from contributing to an autoimmune reaction. It has been reported to reduce the rate of relapses in relapsing-remitting multiple sclerosis by approximately one-half over a two-year period. Medical uses Fingolimod is used in the treatment of the relapsing form of multiple sclerosis. Its effect in those with primary progressive MS is not clear. It may also be used in chronic inflammatory demyelinating polyneuropathy. Adverse effects The most common side effects of fingolimod have been head colds, headache, increased gamma-glutamyl transfer (≤15%), diarrhea (13%), nausea (13%), abdominal pain (11%) and fatigue. A few cases of skin cancer have been reported, which has also been reported in patients taking natalizumab (Tysabri), ...
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Sphingosine-1-phosphate
Sphingosine-1-phosphate (S1P) is a signaling sphingolipid, also known as lysosphingolipid. It is also referred to as a bioactive lipid mediator. Sphingolipids at large form a class of lipids characterized by a particular aliphatic aminoalcohol, which is sphingosine. Production S1P is formed from ceramide, which is composed of a sphingosine and a fatty acid. Ceramidase, an enzyme primarily present in plasma membrane, will convert ceramide to sphingosine. sphingosine is then phosphorylated by sphingosine kinase (SK) isoenzymes. There are two identified isoenzymes, SK1 and SK2. These two enzymes have different tissue distribution. SK1 is highly expressed in spleen, lung and leukocytes, while SK2 is highly expressed in liver and kidney. SK2 is located mainly in the mitochondria, nucleus and the endoplasmic reticulum whereas SK1 is mainly located in cytoplasm and the cell membrane. Metabolism and degradation S1P can be dephosphorylated to sphingosine by sphingosine phosphatases and ...
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Spleen
The spleen is an organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The word spleen comes .σπλήν
Henry George Liddell, Robert Scott, ''A Greek-English Lexicon'', on Perseus Digital Library
The spleen plays very important roles in regard to s (erythrocytes) and the . It removes old red blood cells and holds a reserve of blood, which can be valuable in case of

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Central Nervous System
The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all parts of the bodies of bilaterally symmetric and triploblastic animals—that is, all multicellular animals except sponges and diploblasts. It is a structure composed of nervous tissue positioned along the rostral (nose end) to caudal (tail end) axis of the body and may have an enlarged section at the rostral end which is a brain. Only arthropods, cephalopods and vertebrates have a true brain (precursor structures exist in onychophorans, gastropods and lancelets). The rest of this article exclusively discusses the vertebrate central nervous system, which is radically distinct from all other animals. Overview In vertebrates, the brain and spinal cord are both enclosed in the meninges. The meninges provide a barrier to chemicals dissolv ...
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Hematopoietic
Haematopoiesis (, from Greek , 'blood' and 'to make'; also hematopoiesis in American English; sometimes also h(a)emopoiesis) is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells. In a healthy adult person, approximately – new blood cells are produced daily in order to maintain steady state levels in the peripheral circulation.Semester 4 medical lectures at Uppsala University 2008 by Leif Jansson Process Haematopoietic stem cells (HSCs) Haematopoietic stem cells (HSCs) reside in the medulla of the bone (bone marrow) and have the unique ability to give rise to all of the different mature blood cell types and tissues. HSCs are self-renewing cells: when they differentiate, at least some of their daughter cells remain as HSCs so the pool of stem cells is not depleted. This phenomenon is called asymmetric division. The other daughters of HSCs ( myeloid and lymphoid progenitor cells) can follow any of the other ...
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Lymphoid
The lymphatic system, or lymphoid system, is an organ system in vertebrates that is part of the immune system, and complementary to the circulatory system. It consists of a large network of lymphatic vessels, lymph nodes, lymphatic or lymphoid organs, and lymphoid tissues. The vessels carry a clear fluid called lymph (the Latin word ''lympha'' refers to the deity of fresh water, "Lympha") back towards the heart, for re-circulation. Unlike the circulatory system that is a closed system, the lymphatic system is open. The human circulatory system processes an average of 20 litres of blood per day through capillary filtration, which removes plasma from the blood. Roughly 17 litres of the filtered blood is reabsorbed directly into the blood vessels, while the remaining three litres are left in the interstitial fluid. One of the main functions of the lymphatic system is to provide an accessory return route to the blood for the surplus three litres. The other main function is that of i ...
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Leukocytes
White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from multipotent cells in the bone marrow known as hematopoietic stem cells. Leukocytes are found throughout the body, including the blood and lymphatic system. All white blood cells have nuclei, which distinguishes them from the other blood cells, the anucleated red blood cells (RBCs) and platelets. The different white blood cells are usually classified by cell lineage ( myeloid cells or lymphoid cells). White blood cells are part of the body's immune system. They help the body fight infection and other diseases. Types of white blood cells are granulocytes (neutrophils, eosinophils, and basophils), and agranulocytes (monocytes, and lymphocytes (T cells and B cells)). Myeloid cells (myelocytes) include neutrophils, eosinophils, mast cells, ...
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T Cells
A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their cell surface. T cells are born from hematopoietic stem cells, found in the bone marrow. Developing T cells then migrate to the thymus gland to develop (or mature). T cells derive their name from the thymus. After migration to the thymus, the precursor cells mature into several distinct types of T cells. T cell differentiation also continues after they have left the thymus. Groups of specific, differentiated T cell subtypes have a variety of important functions in controlling and shaping the immune response. One of these functions is immune-mediated cell death, and it is carried out by two major subtypes: CD8+ "killer" and CD4+ "helper" T cells. (These are named for the presence of the cell surface proteins CD8 or ...
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Chemotaxis
Chemotaxis (from '' chemo-'' + ''taxis'') is the movement of an organism or entity in response to a chemical stimulus. Somatic cells, bacteria, and other single-cell or multicellular organisms direct their movements according to certain chemicals in their environment. This is important for bacteria to find food (e.g., glucose) by swimming toward the highest concentration of food molecules, or to flee from poisons (e.g., phenol). In multicellular organisms, chemotaxis is critical to early development (e.g., movement of sperm towards the egg during fertilization) and development (e.g., migration of neurons or lymphocytes) as well as in normal function and health (e.g., migration of leukocytes during injury or infection). In addition, it has been recognized that mechanisms that allow chemotaxis in animals can be subverted during cancer metastasis. The aberrant chemotaxis of leukocytes and lymphocytes also contribute to inflammatory diseases such as atherosclerosis, asthma, and arthr ...
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