Sphingosine 1 Phosphate S1P - Biotech, Pharma and Life Science Channel
Sphingosine-1-phospate (S1P) is a phospholipid released by platelets, mast and other cells. It is now known that S1P stimulates at least five different G-protein coupled receptors (GPCRs): S1P1, S1P2, S1P3, S1P4, and S1P5. Activation of these GPCRs mediates a complex variety of biological responses, such as lymphocyte migration, endothelial cell proliferation, blood vessel constriction, heart rate modulation and others. Selective S1P1 receptor agonists inhibit lymphocyte migration out of lymphoid tissue into the lymphatic and blood circulation, thereby reducing peripheral lymphocyte counts and preventing lymphocyte recruitment to sites of inflammation.
This lymphatic tissue specific mechanism of action offers potential advantages over existing therapies. Sequestration of T cells in lymphoid organs is expected to prevent the processes that contribute to inflammatory diseases such as tissue invasion, local cytokine release, macrophage recruitment, and direct cell killing ? while sparing functions that do not rely on homing mechanisms. These include antibody generation by B lymphocytes, first line immunological protection by neutrophils and monocytes, and antigen-dependent T cell activation and expansion. While a first generation, not specific S1P receptor agonist has advanced in development for multiple sclerosis until phase III, the next generation S1P1 specific receptor agonists have the promise of reduced side effects, e.g. bradycardia via S1P3. Inhibition of S1P lyase in mice caused the concentration of S1P to rise in lymphoid tissues, thereby causing lymphocytes to be retained in the lymphoid tissues. Thus, S1P agonism holds promise for treatment of inflammatory and autoimmune diseases such as multiple sclerosis, psoriasis, asthma, rheumatoid arthritis and transplantation.
In contrast, reducing levels of S1P may have anti-tumor effects because S1P promotes tumor growth by stimulating cell proliferation, metastasis, and cell survival. Corresponding therapeutic approaches are neutralization of S1P levels or inhibition of sphingosine-1-kinase.
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Medical and Biotech [MESH] Definitions
Adp-ribosyl Cyclase
A membrane-bound or cytosolic enzyme that catalyzes the synthesis of CYCLIC ADP-RIBOSE (cADPR) from nicotinamide adenine dinucleotide (NAD). This enzyme generally catalyzes the hydrolysis of cADPR to ADP-RIBOSE, as well, and sometimes the synthesis of cyclic ADP-ribose 2' phosphate (2'-P-cADPR) from NADP.
Deoxyribonuclease (pyrimidine Dimer)
An enzyme which catalyzes an endonucleolytic cleavage near PYRIMIDINE DIMERS to produce a 5'-phosphate product. The enzyme acts on the damaged DNA strand, from the 5' side of the damaged site.
Phosphodiesterase I
A phosphoric diester hydrolase that removes 5'-nucleotides from the 3'-hydroxy termini of 3'-hydroxy-terminated OLIGONUCLEOTIDES. It has low activity towards POLYNUCLEOTIDES and the presence of 3'-phosphate terminus on the substrate may inhibit hydrolysis.
Phosphatidylinositol Diacylglycerol-lyase
A phosphorus-oxygen lyase found primarily in BACTERIA. The enzyme catalyzes the cleavage of a phosphoester linkage in 1-phosphatidyl-1D-myo-inositol to form 1D-myo-inositol 1,2-cyclic phosphate and diacylglycerol. The enzyme was formerly classified as a phosphoric diester hydrolase (EC 3.1.4.10) and is often referred to as a TYPE C PHOSPHOLIPASES. However it is now known that a cyclic phosphate is the final product of this enzyme and that water does not enter into the reaction.
Aryldialkylphosphatase
An enzyme which catalyzes the hydrolysis of an aryl-dialkyl phosphate to form dialkyl phosphate and an aryl alcohol. It can hydrolyze a broad spectrum of organophosphate substrates and a number of aromatic carboxylic acid esters. It may also mediate an enzymatic protection of LOW DENSITY LIPOPROTEINS against oxidative modification and the consequent series of events leading to ATHEROMA formation. The enzyme was previously regarded to be identical with Arylesterase (EC 3.1.1.2).
