Sphingosine-1-phosphate

Sphingosine-1-phosphate (S1P) is a signaling sphingolipid. 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 can be regularly detected in human blood, in particular in association with lipoproteins such as high density lipoprotein (HDL). S1P is a potent messenger molecule. It operates both intra- and intercellularly, thus forming a major agent of signal transduction in various tissues. One of the main targets of S1P are members of the Lysophospholipid receptor family.

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Although S1P is of importance in the entire human body, it might be particularly relevant in the skin. It 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 S1P also is responsible for chemotaxis and angiogenesis.

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

• Sphingosine
• Lipid signaling

References

• Bollag W (2003). "Paradoxical effects of sphingosine-1-phosphate". J Invest Dermatol 120 (4): xiii-xiv. PMID 12648243.

• 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. 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. PMID 12648236.