Lissamine-rhodamine B-dodecanoyl-galactosylceramide Reference: M2204-500 Lissamine-rhodamine B-dodecanoyl-galactosylceramide is a fluorescent labeled glycosphingolipid containing a galactose attached to a ceramide and labeled with a fluorescent lissamine-rhodamine B marker. This fluorescent standard from Matreya is excellent for use in the identification and isolation of cerebrosides in the Krabbe’s disease and other studies.3 Lissamine-rhodamine B dyes have an excitation/emission maxima ~560/580 nm. The fluorescent marker is attached via a 12-carbon linker reducing the interaction of the fluorophore with the sphingolipid. Galactosylcerebrosides are found primarily in neuronal tissues and are a major component of the central nervous system. They are the largest single component of the myelin sheath of nerves and seem to act, along with other molecules, to form part of the structural support of the myelin sheath.1 Cerebrosides are involved in a very wide range of biological activities such as cell agglutination, intracellular communication, cellular development, and antitumor/cytotoxic effects.2 Galactocerebroside can be metabolized into sulfatide which is also abundant in the nervous system and myelin sheath. Due to the relatively high melting point of cerebrosides (much greater than physiological body temperature) they have a paracrystalline structure. Krabbe’s disease (globoid cell leukodystrophy) is characterized by a deficiency in the enzyme galactocerebrosidase, which is responsible for degrading galactocerebroside. This leads to an accumulation of cerebroside and psychosine which can result in demyelination of nerves and loss of axonal conductivity.
N-Hexanoyl-biotin-lactosylceramide Reference: M2205-1 N-Hexanoyl-biotin-lactosylceramide contains a biotin unit attached to the amine of the sphingosine moiety via a hexanoic acid linker and is ideal for use in sphingolipid studies. The biotin structure allows for the attachment of the lactosylceramide to streptavidin, avidin, or any other biotin binding protein making it extremely useful for substrate and toxin detection1. The avidin-biotin complex is the strongest known non-covalent interaction between a protein and ligand. The formation of the bond is very rapid and once formed is stable with regards to pH, temperature, organic solvents, and denaturing agents. The biotin label is attached via a 6-carbon linker reducing the interaction of the biotin with the lactosylceramide. Lactosylceramide is the precursor of many other glycosphingolipids and also functions as a second messenger and protein receptor, making it a very important organic molecule. Many cellular processes are dependent on lactosylceramide since it is the substrate for neutral oligoglycosylceramides, sulfatides and gangliosides, all of which have their own vital functions. Lactosylceramide also helps to stabilize the lipid membrane, activate receptor molecules and acts as a receptor for certain bacteria and toxins. Its role as a second messenger has been found to be vital and dysfunctions in its processes can lead to cancer and inflammation since it is critical to neutrophil activity and in activating anti-inflammatory responses.2 Other examples of lactosylceramide second messenger functions are tumor necrosis factor alpha and platelet-derived growth factor. A deficiency in the enzyme responsible for hydrolyzing the galactose of lactosylceramide leads to lactosylceramidosis, which is characterized by an accumulation of lactosylceramide that causes a primary neurological disorder.3 Lactosylceramide is also important in the activation of platelet/endothelial cell adhesion molecule-1 which causes adhesion and diapedesis of monocytes/lymphocytes.4
N-Hexanoyl-biotin-sulfatide Reference: M2207-1 N-Hexanoyl-biotin-sulfatide contains a biotin unit attached to the amine of the sphingosine via a hexanoic acid linker and is ideal for use in sphingolipid studies. The biotin structure allows for the attachment of the sulfatide to streptavidin, avidin, or any other biotin binding protein making it extremely useful for substrate and toxin detection1. The avidin-biotin complex is the strongest known non-covalent interaction between a protein and ligand. The formation of the bond is very rapid and once formed is stable with regards to pH, temperature, organic solvents, and denaturing agents. The biotin label is attached via a 6-carbon linker reducing the interaction of the biotin with the sulfo-galactose. Sulfatide is a type of sulfolipid that is found primarily in the central nervous system and is a myelin-specific sphingolipid. A deficiency of sulfatide in white and gray matter has been associated with Alzheimer’s disease and other types of dementia. Apoliprotein E plays an important regulating role in the metabolism of sulfatides.2 The production of anti-sulfatide antibodies in the cerebrospinal fluid, leading to a deficiency in sulfatides, may be a cause of degeneration of the myelin sheath, leading to multiple sclerosis and other demyelinating diseases.3 Metachromatic leukodystrophy is an inherited disorder characterized by a deficiency of the lysosomal enzyme arylsulfatase A and the subsequent accumulation of sulfatide in neural and visceral tissues.4 Sulfatide also regulates the differentiation of oligodendroblasts. Central nervous system (CNS) myelin is strongly inhibitory to growing axons and sulfatides present in the myelin of the CNS have been identified as major myelin-associated axon growth inhibitors.5 Sulfatides in the myelin, especially cis-tetracosenoyl-sulfatides, stimulate a distinct population of CD1d-restricted natural killer T cells giving these sulfatides important implications for the design of therapeutics that target T cells reactive for myelin glycolipids in autoimmune diseases of the central nervous system.6
N-Hexanoyl-biotin-phytosphingosine Reference: M2211-5 This phytoceramide analogue contains a biotin unit attached to the amine of the phytosphingosine moiety via a hexanoic acid linker and is ideal for use in sphingolipid studies. The biotin structure allows for attachment of the ceramide to streptavidin and avidin making it extremely useful for binding to substrates and for toxin detection1. Phytosphingosine is a long-chain sphingoid base having important cellular functions such as signaling, cytoskeletal structure, cellular cycle, and heat stress response. It is found largely in mammals, plants, and yeast. Phytosphingosine has seen much use in cosmetics due to its effects on the skin such as reducing inflammation by inhibiting the expression of the allergic cytokines IL-4 and TNF-α and the activation of the transcription factors NF-jB and c-jun in histamine-stimulated skin tissues.2 Phytosphingosine can lead to apoptosis via two distinct pathways and has been investigated as a possible cancer therapeutic treatment. Phytoceramides (fatty acid acylated to Phytosphingosine) are distributed at the microvillous membrane of the epithelial cells of the small intestine. Crypt cells and the adjacent epithelial cells produce phytosphingoglycolipids in much greater quantities than more differentiated epithelial cells.3 The kidney and skin also contain phytosphingoglycolipids although in much lower concentrations than in the small intestine. Phytoceramides form part of the water barrier lipids of the skin. 2-hydroxytetracosanoyl-phytoceramide has recently been shown to have immunostimulating effects in humans.4 Phytoceramides have lately been studied in regards to their role in the central nervous system and have been found to have important functions in neuroprotection.5
N-Hexanoyl-biotin-D-erythro-dihydrosphingosine Reference: M2212-5 This dihydroceramide analogue contains a biotin unit attached to the amine of the dihydrosphingosine moiety via a hexanoic acid linker and is ideal for use in sphingolipid studies. The biotin structure allows for attachment of the ceramide to streptavidin and avidin making it extremely useful for binding to substrates and for toxin detection1. 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 and is subsequently converted to ceramide via the enzyme dihydroceramide desaturase or into phytosphingosine via the enzyme C4-hydroxylase.2 Inhibition of ceramide synthase by some fungal toxins (such as fumonisin B1) causes an accumulation of dihydrosphingosine and sphinganine-1-phosphate and a decrease in dihydroceramide and other dihydrosphingolipids, leading to a number of diseases including oesophageal cancer.3 The dihydroceramide desaturase inhibitor N-(4-Hydroxyphenyl)-retinamide (4-HPR) has been tested as an anti-cancer agent; It inhibits 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.4 Oxidative stress in cells causes an increase in the amount of dihydroceramide by potently inhibiting the desaturase enzyme.5 Dihydroceramide inhibits the formation of channels by ceramides and may thus reduce ceramide induced apoptosis in cells.6 While ceramide is well known for promoting apoptosis, dihydroceramide has long been considered to be inactive. However, there has recently been evidence that an accumulation of dihydroceramide can induce cell cycle arrest.7