Category: Reagents

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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.

AS-1269574

Reference: 10626-10

An agonist of GPR199 that is effective both in isolated cells and in vivo; increases cAMP levels in HEK293 cells transfected with human GPR119 (EC50 = 2.5 μM) and promotes glucose-stimulated insulin secretion in mice (100 mg/kg)

SEA0400

Reference: A3811-50

Specific inhibitor of Na+/Ca2+ exchange

N-(32-Linoleoyloxy-dotriacontanoyl)-sphingosine-D9

Reference: M2208-1

This product is a high purity omega-esterified ceramide that is ideal as a standard and for studies involving skin-barrier lipids. Omega-esterified ceramides are found almost exclusively in the epidermal layer, especially the stratum corneum. The stratum corneum is the outermost cellular layer of the epidermis and functions as the permeability barrier in mammals. It contains 12 extractable ceramide fractions containing sphingosine, 6-hydroxysphingosine, dihydrosphingosine and phytosphingosine bases.1,2 The omega-esterified ceramides are formed from glucosylceramide and sphingomyelin in special lamellar bodies in epidermal cells from which they are excreted into the extracellular domain of the outermost cell layer of the epidermis. Mammalian skin contains significant amounts of sphingolipids (as much as 50% of the total lipids), particularly very long chain linoleoyl esterified ceramide and glucosylceramide (also called O-acylceramide and O-acylglucosylceramide). These lipids, which are mostly found in the extracellular domains, are vital to the water permeability barrier to prevent lethal loss of water and pathogen invasion. The omega-esterified ceramides can be covalently bound to proteins of the cornified envelope where they form a hydrophobic layer. A deficiency of linoleoyl omega-esterified ceramides is strongly correlated with skin diseases such as psoriasis and atopic dermatitis.3

AS-1269574

Reference: 10626-25

An agonist of GPR199 that is effective both in isolated cells and in vivo; increases cAMP levels in HEK293 cells transfected with human GPR119 (EC50 = 2.5 μM) and promotes glucose-stimulated insulin secretion in mice (100 mg/kg)

Seocalcitol

Reference: A3814-1

Vitamin D receptor agonist

13C6-Glucosylsphingosine

Reference: M2209-1

Glucosylsphingosine is the lyso-derivative of the common glycolipid glucocerebroside. This product is a stable isotope labeled standard containing six carbon-13 units on the glucose moiety. Glucosylceramide and glucosylsphingosine are important biological species that are the precursors for many complex glycosphingolipids. These lipids are involved in critical cellular functions such as cellular proliferation, differentiation, adhesion, signal transduction, cell-to-cell interactions, tumorigenesis, and metastasis. One of the most important roles of glucosylsphingosine is as a biomarker for the lysosomal storage disorder Gaucher disease. Gaucher disease is characterized by an accumulation of glucocerebroside due to a deficiency in the enzyme glucocerebrosidase and it has now been found that glucosylsphingosine also accumulates in this disease.1 This accumulation of glucosylsphingosine contributes to neuronal dysfunction and destruction in patients with neuronopathic Gaucher disease2 and it has been found to be a potent inhibitor of glucocerebrosidase. At least some instances of Gaucher disease also have a deficiency in the activity of glucopsychosine beta-glucosidase, the enzyme responsible for cleaving off the glucose of glucopsychosine and glucocerebroside. Like glucocerebroside and galactocerebroside, glucosylsphingosine can increase Ca2 + mobilization from intracellular stores although it uses a different mechanism.3 Conduritol B epoxide (CBE), an inhibitor of beta-glucosidase, and l-phenyl-2-decanoylamino-3-morpholino-l-propanol (PDMP), an inhibitor of glucosylceramide synthase, can be used to create a model of Gaucher disease and consequently an accumulation of glucosylsphingosine.4

AS-1269574

Reference: 10626-5

An agonist of GPR199 that is effective both in isolated cells and in vivo; increases cAMP levels in HEK293 cells transfected with human GPR119 (EC50 = 2.5 μM) and promotes glucose-stimulated insulin secretion in mice (100 mg/kg)

Seocalcitol

Reference: A3814-5

Vitamin D receptor agonist

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