N-omega-CD3-Octadecanoyl monosialoganglioside GM2 (NH4+ salt) Reference: M2051-250 This deuterated ganglioside is ideal for the identification of gangliosides in samples and biological systems using mass spectrometry.1 Gangliosides2 are acidic glycosphingolipids that form lipid rafts in the outer leaflet of the cell plasma membrane, especially in neuronal cells in the central nervous system.3 They participate in cellular proliferation, differentiation, adhesion, signal transduction, cell-to-cell interactions, tumorigenesis, and metastasis.4 GM2 regulates the function of ciliary neurotrophic factor receptors. The accumulation of GM2 (due to a deficiency in beta-hexosaminidase) has characterized Tay-Sachs disease (due to a mutation in the gene HEXA) and Sandhoff disease (due to a mutation in the gene HEXB). A mutation in the GM2A gene results in GM2 activator deficiency that also leads to accumulation of GM2.5
N-omega-CD3-Octadecanoyl monosialoganglioside GM3 (NH4+ salt) Reference: M2052-250 This deuterated ganglioside is ideal for the identification of gangliosides in samples and biological systems using mass spectrometry.1 Gangliosides2 are acidic glycosphingolipids that form lipid rafts in the outer leaflet of the cell plasma membrane, especially in neuronal cells in the central nervous system.3 They participate in cellular proliferation, differentiation, adhesion, signal transduction, cell-to-cell interactions, tumorigenesis, and metastasis.4 The accumulation of gangliosides has been linked to several diseases including Tay-Sachs and Sandhoff disease. GM3 is the main ganglioside of human fibroblasts and can regulate fibroblast and epidermal growth factors5 and is also able to regulate the adhesion and migration of several carcinoma cell lines. GM3 was also shown to inhibit tumor cell invasion. GM3 can induce human promyelocytic leukemia HL-60 cells to differentiate to monocyte/macrophage lineage instead of granulocytes.6
N-omega-CD3-Octadecanoyl disialoganglioside GD3 (NH4+ salt) Reference: M2054-500 Gangliosides1 are acidic glycosphingolipids that form lipid rafts in the outer leaflet of the cell plasma membrane, especially in neuronal cells in the central nervous system.2 They participate in cellular proliferation, differentiation, adhesion, signal transduction, cell-to-cell interactions, tumorigenesis, and metastasis. The accumulation of gangliosides has been linked to several diseases including Tay-Sachs and Sandhoff disease. GD3 is predominantly expressed during neuronal development and its expression becomes very limited in adult tissues. GD3 expression is unusually high in basal cell carcinomas and malignant melanomas and is thought to be a human melanoma-specific antigen. Although GD3 is not immunogenic it has been investigated as a tool for immunotargeting human melanoma cells.3 Over expression of GD3 has led to apoptosis by recruiting mitochondria to apoptotic pathways and suppressing NF-κB activation and subsequent κB-dependent gene induction.4 Increased levels of GD3 have also been found to be associated with proliferative diseases, such as atherosclerosis. A recent study has demonstrated that inhibition of GD3 synthase, thereby decreasing levels of GD3, has neuroprotective properties in a Parkinson's model and may warrant further investigation as a therapeutic target.5 Stable isotope labeled GD3 is a new mass spectrometry internal standard that can greatly enhance ganglioside studies.6
N-Hexadecanoyl-D9 (13,13,14,14,15,15,16,16,16)-monosialoganglioside GM1 (NH4+... Reference: M2057-500 Gangliosides1 are acidic glycosphingolipids that form lipid rafts in the outer leaflet of the cell plasma membrane, especially in neuronal cells in the central nervous system.2 They participate in cellular proliferation, differentiation, adhesion, signal transduction, cell-to-cell interactions, tumorigenesis, and metastasis.3 The accumulation of gangliosides has been linked to several diseases including Tay-Sachs and Sandhoff disease. An autoimmune response against gangliosides can lead to Guillain-Barre syndrome. GM1 stimulates neuronal sprouting and enhances the action of nerve growth factor (NGF) by directly and tightly associating with Trk, the high-affinity tyrosine kinase-type receptor for NGF. It is the specific cell surface receptor for cholera toxin.4
N-Hexadecanoyl-D9 (13,13,14,14,15,15,16,16,16)-monosialoganglioside GM2 (NH4+... Reference: M2058-500 Gangliosides1 are acidic glycosphingolipids that form lipid rafts in the outer leaflet of the cell plasma membrane, especially in neuronal cells in the central nervous system.2 They participate in cellular proliferation, differentiation, adhesion, signal transduction, cell-to-cell interactions, tumorigenesis, and metastasis.3 The accumulation of gangliosides has been linked to several diseases including Tay-Sachs and Sandhoff disease. An autoimmune response against gangliosides can lead to Guillain-Barre syndrome. GM1 stimulates neuronal sprouting and enhances the action of nerve growth factor (NGF) by directly and tightly associating with Trk, the high-affinity tyrosine kinase-type receptor for NGF. It is the specific cell surface receptor for cholera toxin.4
N-Hexadecanoyl-D9 (13,13,14,14,15,15,16,16,16)-monosialoganglioside GM3... Reference: M2059-500 This deuterated ganglioside is ideal for the identification of gangliosides in samples and biological systems using mass spectrometry.1 Gangliosides2 are acidic glycosphingolipids that form lipid rafts in the outer leaflet of the cell plasma membrane, especially in neuronal cells in the central nervous system.3 They participate in cellular proliferation, differentiation, adhesion, signal transduction, cell-to-cell interactions, tumorigenesis, and metastasis.4 The accumulation of gangliosides has been linked to several diseases including Tay-Sachs and Sandhoff disease. GM3 is the main ganglioside of human fibroblasts and can regulate fibroblast and epidermal growth factors5 and is also able to regulate the adhesion and migration of several carcinoma cell lines. GM3 was also shown to inhibit tumor cell invasion. GM3 can induce human promyelocytic leukemia HL-60 cells to differentiate to monocyte/macrophage lineage instead of granulocytes.6
D-erythro-Sphingosine, D9 Reference: M2079-1 This synthetic D-erythro-sphingosine contains nine deuterium atoms making it an ideal stable isotope-labeled standard for lipidomic studies using mass spectrometry. Stable isotope-labeled tracers are ideal for studies involving the metabolism and various metabolites of a lipid and can be used for the quantitative evaluation of major lipid pathways.1 Lipidomics has shown great success in the use of deuterium labeled compounds in identifying and quantifying individual molecular species by the use of tandem mass spectrometry.2 This deuterated sphingosine can also be used in the preparation of sphingolipids that are labeled on the sphingosine chain. In this way deuterated ceramides can be prepared that will not lose their label if the fatty acid is cleaved off in vivo and replaced by an alternate fatty acid. Sphingosine is a characteristic structural unit of many sphingolipids such as ceramides, gangliosides, globosides, sulfatides, sphingomyelin, and others.3,4 It is most abundant in nervous tissue and cell membranes. Sphingosine with an 18- carbon chain and a double bond at carbon 4 is the most abundant sphingosine in animal tissues. Lysosphingolipids inhibit protein kinase C activity resulting in the pathogenesis of sphingolipidoses such as Krabbe's disease and Gaucher's disease.5 Sphingosine can be phosphorylated via two kinases to form sphingosine-1-phosphate, which has important signaling functions. While sphingosines and ceramides can induce apoptosis,6 sphingosine-1-phosphate can promote cell survival or proliferation. Sphingosine has also been shown to cause an increase in the cytoplasmic calcium level of cells.
D-erythro-C17-Sphingosine Reference: M2082-5 This synthetic sphingosine contains an odd number of carbons with a natural D-erythro stereocenter making it an ideal internal standard for sphingolipidomic studies using HPLC and mass spectrometry. Mammalian cells contain mostly Derythro sphingosines having C18 and C20 bases with a smaller amount of C16 bases. Some bacteria and fungi have predominantly C16 or even shorter sphingosine bases. C17 sphingosine bases are easily separated by reverse phase HPLC and readily identified by mass spectrometry. They are also usually absent from, or present in low amounts in, natural systems reducing the need for background subtractions. Due to its natural stereochemistry and very similar physical characteristics to natural sphingosines this product represents the extraction and signal intensity of natural sphingosine in most applications making it a useful choice as an internal standard. This product is also active in biosynthesis and can be incorporated into more complex sphingolipids by cellular enzymes making it useful for metabolic studies. Sphingosine is the characteristic structural unit of sphingolipids such as ceramides, gangliosides, globosides, sulfatides, sphingomyelin, and others.1,2 It is most abundant in nervous tissue and cell membranes. Sphingosine with an 18- carbon chain and a double bond at carbon 4 is the most abundant sphingosine in animal tissues. Lysosphingolipids (sphingolipids containing a free amine on carbon 3) inhibit protein kinase C activity resulting in the pathogenesis of sphingolipidoses such as Krabbe's disease and Gaucher's disease.3 Sphingosine can be phosphorylated via two kinases to form sphingosine-1-phosphate, which has important signaling functions. While sphingosines and ceramides can induce apoptosis,4 sphingosine-1-phosphate can promote cell survival or proliferation. Sphingosine has also been shown to cause an increase in the cytoplasmic calcium level of cells.
N-1-13C-Hexadecanoyl-D-erythro-sphingosylphosphorylcholine Reference: M2200-1 This product is a stable isotope analog of sphingomyelin containing a 13C on the fatty acid portion of ceramide and is ideal for use as a standard. Sphingomyelin is found in mammalian cell membranes, especially in the membranes of the myelin sheath. It is the most abundant sphingolipid in mammals and is thought to be found mostly in the exoplasmic leaflet of the membrane although there is also evidence of a sphingomyelin pool in the inner leaflet of the membrane. It is involved in signal transduction and apoptosis.1 An improper ratio of sphingomyelin to ceramide has been shown to be a factor in Niemann-Pick disease2 and neonatal respiratory distress syndrome.3 However, the ratio of sphingomyelin to ceramide is different for different cell types.4 Sphingomyelin is an important amphiphilic component when plasma lipoprotein pools expand in response to large lipid loads or metabolic abnormalities.5 N-hexanoyl-sphingosylphosphorylcholine has been used to enhance the uptake of anti-tumor drugs by cancer cells, thereby increasing the cytotoxicity towards those cancer cells.6
N-omega-CD3-Octadecanoyl-D-erythro-sphingosine Reference: M2201-1 This product is a well-defined ceramide containing a deuterated stearic acid acylated to the sphingosine base making it an ideal stable isotope-labeled standard for lipidomic studies using mass spectrometry. Stable isotope-labeled tracers are ideal for studies involving the metabolism and various metabolites of a lipid and can be used for the quantitative evaluation of major lipid pathways.1 Lipidomics has shown great success in the use of deuterium labeled compounds in identifying and quantifying individual molecular species by the use of tandem mass spectrometry.2 Ceramide is a fatty acid amide of sphingosine that has many important biological functions and is the precursor for many complex glycosphingolipids. Ceramide functions as a precursor in the synthesis of sphingomyelin, glycosphingolipids, and of free sphingosine and fatty acids. The sphingosine can be phosphorylated to form sphingosine-1-phosphate. Two of ceramide’s metabolites, sphingosine- 1-phosphate and glucosylceramide, produce cell proliferation and other cellular functions.3 Ceramide exerts numerous biological effects, including induction of cell maturation, cell cycle arrest, terminal cell differentiation, cell senescence, and cell death.4 Because of these effects ceramide has been investigated for its use in cancer treatment and many potential approaches to cancer therapy have been presented.5 Other effects include producing reactive oxygen in mitochondria (followed by apoptosis) and stimulating phosphorylation of certain proteins (especially mitogen activated protein). It also stimulates some protein phosphatases (especially protein phosphatase 2A) making it an important controller of protein activity.
N-omega-CD3-Octadecanoyl-D-erythro-dihydrosphingosine Reference: M2202-1 This product is a well-defined dihydroceramide containing a deuterated stearic acid acylated to a sphinganine base making it an ideal stable isotope-labeled standard for lipidomic studies using mass spectrometry. Stable isotope-labeled tracers are ideal for studies involving the metabolism and various metabolites of a lipid and can be used for the quantitative evaluation of major lipid pathways.1 Lipidomics has shown great success in the use of deuterium labeled compounds in identifying and quantifying individual molecular species by the use of tandem mass spectrometry.2 Dihydroceramide is a critical intermediate in the de novo synthesis of ceramide, leading to many complex sphingolipids. It is synthesized by the acylation of sphinganine (dihydrosphingosine) and is subsequently converted to ceramide via the enzyme dihydroceramide desaturase or into phytosphingosine via the enzyme C4-hydroxylase.3 Inhibition of ceramide synthase by some fungal toxins (such as fumonisin B1) causes an accumulation of sphinganine and sphinganine-1- phosphate and a decrease in dihydroceramide and other dihydrosphingolipids, leading to a number of diseases including oesophageal cancer.4 The dihydroceramide desaturase inhibitor N-(4-Hydroxyphenyl) retinamide (4-HPR) has been tested as an anti-cancer agent by inhibiting the dihydroceramide desaturase enzyme in cells resulting in a high concentration of dihydroceramide and dihydro-sphingolipids and this is thought to be the cause of its anti-cancer effects.5 Oxidative stress in cells causes an increase in the amount of dihydroceramide by potently inhibiting the desaturase enzyme.6 Dihydroceramide inhibits the formation of channels by ceramides and may thus reduce ceramide induced apoptosis in cells.7
N-omega-CD3-Octadecanoyl-D-erythro-sphingosine-1-phosphate Reference: M2206-1 This deuterated ceramide-1-phosphate is ideal as a mass spectrometry standard and for in vivo and in vitro investigations. Ceramide-1-phosphate is one of several important phosphosphingolipids in mammalian cells and it is generated by the phosphorylation of ceramide by the enzyme ceramide kinase. Ceramide-1-phosphate is currently attracting much attention in research due to its important cellular functions like its role in inflammation, as a novel second messenger, and its involvement in cellular processes like phagocytosis, potassium channel function, inflammatory responses, cell survival, and tumorigenesis. The first reported biological action of ceramide-1-phosphate was its ability to stimulate DNA synthesis and cell division. Ceramide-1-phosphate was also found to be mitogenic for both fibroblasts and macrophages. The mitogenic effect of ceramide-1-phosphate is dependent on its intracellular ability to stimulate reactive oxygen specie production in macrophages via the enzyme NADPH oxidase. This enzyme is downstream of PKC-α and cPLA(2)-α in this pathway. Another important function of ceramide-1-phophate is its promotion of cell survival. Ceramide-1-phosphate stimulates the phosphatidylinositol 3-kinase (PI3-K)/protein kinase B (PKB) pathway, a major mechanism whereby growth factors promote cell survival. It is probable that ceramide-1-phosphate blocks apoptosis by stimulating the PI3-K/PKB/NFkappaB pathway and thereby maintaining the production of antiapoptotic Bcl-X(L). Based on these and previous findings it has been proposed that the inhibition of acid sphingomyelinase and the subsequent decrease in ceramide levels would allow cell signaling through stimulation of the PI3-K/PKB pathway to promote cell survival.