Community hub
Recent from talks
Knowledge base stats:
Talk channels stats:
Members stats:
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.
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 mammalian 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 mitochondrion, nucleus and the endoplasmic reticulum, whereas SK1 is mainly located in cytoplasm and the cell membrane.
S1P can be dephosphorylated to sphingosine by sphingosine phosphatases and can be irreversibly degraded by an enzyme, sphingosine phosphate lyase.
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 sphingosine-1-phosphate receptors (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, orchestrating how immune cells migrate within the arterial wall. 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. S1P has also been shown to directly suppress TLR mediated immune response from T cells.
A research team, led by a scientist at Weill Cornell Medical College, has discovered that red blood cells perform a second vital function: angiogenesis. Given its role in creating new blood vessels, scientists recognize S1P as vital to human health — and a player in some diseases, such as cancer. And although S1P is known to be blood borne, no one realized until this study that S1P is supplied by red blood cells to control blood vessel growth.
The levels of S1P (in a range of 5–40 μmol/L) are 5 to 10 times up-regulated in ovarian cancer patients' ascites. S1P at this physiological concentration stimulates migration and invasion of epithelial ovarian cancer cells but inhibits migration of normal ovarian surface epithelial cells. Most (more than 90%) ovarian cancers arise from the epithelium of the ovary. Therefore, extracellular S1P could have an important role in cancer progression by promoting migration of epithelial ovarian cancer cells.
Hub AI
Sphingosine-1-phosphate AI simulator
(@Sphingosine-1-phosphate_simulator)
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.
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 mammalian 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 mitochondrion, nucleus and the endoplasmic reticulum, whereas SK1 is mainly located in cytoplasm and the cell membrane.
S1P can be dephosphorylated to sphingosine by sphingosine phosphatases and can be irreversibly degraded by an enzyme, sphingosine phosphate lyase.
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 sphingosine-1-phosphate receptors (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, orchestrating how immune cells migrate within the arterial wall. 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. S1P has also been shown to directly suppress TLR mediated immune response from T cells.
A research team, led by a scientist at Weill Cornell Medical College, has discovered that red blood cells perform a second vital function: angiogenesis. Given its role in creating new blood vessels, scientists recognize S1P as vital to human health — and a player in some diseases, such as cancer. And although S1P is known to be blood borne, no one realized until this study that S1P is supplied by red blood cells to control blood vessel growth.
The levels of S1P (in a range of 5–40 μmol/L) are 5 to 10 times up-regulated in ovarian cancer patients' ascites. S1P at this physiological concentration stimulates migration and invasion of epithelial ovarian cancer cells but inhibits migration of normal ovarian surface epithelial cells. Most (more than 90%) ovarian cancers arise from the epithelium of the ovary. Therefore, extracellular S1P could have an important role in cancer progression by promoting migration of epithelial ovarian cancer cells.