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Sphingosine-1-phosphate
Sphingosine-1-phosphate.GIF
Identifiers
CAS number 26993-30-6
PubChem 5283560
MeSH sphingosine+1-phosphate
Properties
Molecular formula C18H38NO5P
Molar mass 379.472
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Sphingosine-1-phosphate (S1P) is a signaling sphingolipid. 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. Sphingosine can be released from ceramides, a process catalyzed by the enzyme ceramidase. Phosphorylation of sphingosine is catalyzed by sphingosine kinase, an enzyme ubiquitously found in the cytosol and endoplasmatic reticulum of various types of cells. S1P can be cleaved by sphingosine phosphatase.

S1P is a blood borne lipid mediator, in particular in association with lipoproteins such as high density lipoprotein (HDL). It is less abundant in tissue fluids. This is referred to as the S1P gradient which seems to have biological significance in immune cell trafficking.

Originally thought as an intracellular second messenger, it was discovered to be an extracellular ligand for G protein-coupled receptor S1PR1 in 1998. It is now known that S1P receptors are members of the Lysophospholipid receptor family. There are five described to date. Most of the biological effects of S1P are mediated by signaling through the cell surface receptors.

Although S1P is of importance in the entire human body, it is a major regulator of vascular and immune systems. In addition, it might be relevant in the skin. In the vascular system, S1P regulates angiogenesis, vascular stability and permeability. In the immune system, it is now recognized as a major regulator of trafficking of T- and B-cells. S1P interaction with its receptor S1PR1 is needed for the egress of immune cells from the lymphoid organs (such as thymus and lymph nodes) into the lymphatic vessels. Inhibition of S1P receptors was shown to be critical for immunomodulation. Currently, an experimental compound, FTY720, is undergoing clinical trials to determine if it is useful in controlling the autoimmune reactions in multiple sclerosis.

In addition, S1P modulates the proliferation of skin cells. This in particular applies to keratinocytes while fibroblasts are not addressed in this way. Apart from cell growth and differentiation While S1P suppresses epidermal proliferation as the glucocorticoids do it differs from them in so far as proliferation of dermal fibroblasts is not reduced. In fact, S1P even activates fibroblast-derived extracellular matrix protein production. Due to the hyperproliferative action against epidermal cells S1P has been considered as an active pharmaceutical ingredient for hyperproliferative skin diseases, in particular psoriasis vulgaris and acne vulgaris.

Although S1P is active at very low concentrations, bioavailability of the compound in human skin is a concern. Therefore a topical formulation based on specific drug carriers has been considered inevitable.

See also

References

Baumrucker, T et al. (2007). "FTY720, an immunomodulatory sphingolipid mimetic: translation of a novel mechanism into clinical benefit in multiple sclerosis.". Expert Opin Investig Drugs 16 (3): 283–289. doi:10.1517/13543784.16.3.283. PMID 17302523.  

  • Manggau M et al. (2001). "1Alpha,25-dihydroxyvitamin D3 protects human keratinocytes from apoptosis by the formation of sphingosine-1-phosphate". J Invest Dermatol 117 (5): 1241–9. doi:10.1046/j.0022-202x.2001.01496.x. PMID 11710939.  
  • Vogler R et al. (2003). "Sphingosine-1-phosphate and its potentially paradoxical effects on critical parameters of cutaneous wound healing". J Invest Dermatol 120 (4): 693–700. doi:10.1046/j.1523-1747.2003.12096.x. PMID 12648236.  
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