Disease relevance of 2-[[(E,2R,3S)-2-amino-3-hydroxy-octadec-4-enoxy]-hydroxy-phosphoryl]oxyethyl-trimethyl-azanium

• Sphingosylphosphocholine, a signaling molecule which accumulates in Niemann-Pick disease type A, stimulates DNA-binding activity of the transcription activator protein AP-1 [1].
• When cultured with Shewanella alga NS-589 in synthetic medium, sphingomyelin was found to be efficiently converted by sphingomyelin deacylase to sphingosylphosphocholine [2].
• Metabolism and neurite promoting effect of exogenous sphingosylphosphocholine in cultured murine neuroblastoma cells [3].
• Since lysosphingolipids have been implicated in the biochemical pathogenesis of other genetic lysosomal sphingolipidoses, the occurrence of sphingosylphosphorylcholine (lysosphingomyelin) was specifically investigated in brain and extraneural tissues, using an HPLC method with fluorescent detection of orthophtalaldehyde derivatives [4].

Psychiatry related information on 2-[[(E,2R,3S)-2-amino-3-hydroxy-octadec-4-enoxy]-hydroxy-phosphoryl]oxyethyl-trimethyl-azanium

• 5. Lysosphingomyelin may be of clinical use in allaying progressive Group 1 mGluR-induced hippocampal cognitive and motor disorders including Alzheimer's disease, brain seizure, and stroke [5].

High impact information on 2-[[(E,2R,3S)-2-amino-3-hydroxy-octadec-4-enoxy]-hydroxy-phosphoryl]oxyethyl-trimethyl-azanium

• We report that both lysosphingomyelin (D-erythro-sphingosyl-phosphorylcholine; SPC) and sphingosine 1-phosphate (SPP) activate IK(ACh) in guinea pig atrial myocytes through the same receptor with an EC50 of 1.5 and 1.2 nM, respectively [6].
• Sphingosylphosphocholine reduces the calcium ion requirement for activating tissue transglutaminase [7].
• We found that sphingosylphosphocholine (lyso-SM) was the only lipid to activate transglutaminase at low Ca2+ concentrations [7].
• Purification was performed by chromatography on DEAE anion-exchange, Q-Sepharose Fast Flow, hydroxylapatite, sphingosylphosphocholine affinity, and Superose 12 gel filtration columns [8].
• Re-evaluation of primary structure, topology, and localization of Scamper, a putative intracellular Ca2+ channel activated by sphingosylphosphocholine [9].

Biological context of 2-[[(E,2R,3S)-2-amino-3-hydroxy-octadec-4-enoxy]-hydroxy-phosphoryl]oxyethyl-trimethyl-azanium

• However, as a consequence of the epimerization at C-3 of SPC in both acid hydrolysis procedures, the resulting N-acyl SM consisted of mixtures of D-erythro and L-threo sphingomyelins [10].
• Spingosylphosphorylcholine (lysosphingomyelin or SPC) is an effective and broad spectrum cell growth promoting agent and a candidate for evaluation on wound healing [11].
• We previously demonstrated that the sphingolipid, sphingosylphosphocholine (SPC) increased DNA binding activity of AP-1 proteins accompanying cellular proliferation [12].

Anatomical context of 2-[[(E,2R,3S)-2-amino-3-hydroxy-octadec-4-enoxy]-hydroxy-phosphoryl]oxyethyl-trimethyl-azanium

• Sphingosylphosphocholine modulates the ryanodine receptor/calcium-release channel of cardiac sarcoplasmic reticulum membranes [13].
• Sphingosylphosphocholine (SPC) modulates Ca2+ release from isolated cardiac sarcoplasmic reticulum membranes; 50 microM SPC induces the release of 70 80% of the accumulated calcium [13].
• Sphingosylphosphocholine is a naturally occurring lipid mediator in blood plasma: a possible role in regulating cardiac function via sphingolipid receptors [14].
• Interestingly, only SPC induced neurite outgrowth and changed the lipid composition, modifying the amounts of cholesterol, sphingomyelin (SM) and ganglioside GM3 in all cell lines [15].
• The effect of SPC on these cell lines was comparable to the effect of N-acetyl SPC (NAcSPC) rather than that of SM [15].

Associations of 2-[[(E,2R,3S)-2-amino-3-hydroxy-octadec-4-enoxy]-hydroxy-phosphoryl]oxyethyl-trimethyl-azanium with other chemical compounds

• 2. Recent in vitro research has demonstrated that a natural cationic amphiphile in the brain, lysosphingomyelin, may be able to prevent neuronal degeneration by repressing phosphosinositidase-C overactivation induced by excessive excitation of the metabotropic glutamate receptor [5].
• Sphingosylphosphorylcholine, lysosphingomyelin, elicited a rapid Ca2+ release from both cerebral and cerebellar microsomes [16].

Gene context of 2-[[(E,2R,3S)-2-amino-3-hydroxy-octadec-4-enoxy]-hydroxy-phosphoryl]oxyethyl-trimethyl-azanium

• The mRNA of Scamper, a putative intracellular calcium channel activated by sphingosylphosphocholine, contains a long 5' transcript leader with several upstream AUGs [17].
• Lysosphingomyelin has been implicated in the nervous system involvement associated with type A disease in humans and accumulations of the NPC-1 protein and apolipoprotein D have been found in murine NP-C brain [18].

Analytical, diagnostic and therapeutic context of 2-[[(E,2R,3S)-2-amino-3-hydroxy-octadec-4-enoxy]-hydroxy-phosphoryl]oxyethyl-trimethyl-azanium

• By using a combination of HPLC and TLC techniques with matrix-assisted laser desorption ionization-time-of-flight MS, we purified and identified sphingosine 1-phosphate (SPP) and sphingosylphosphocholine (SPC) as the plasma and serum factors responsible for activating the inwardly rectifying K+ channel (I(K)) [14].
• Blue Sepharose, sphingosylphosphocholine Sepharose chromatography and FPLC-Mono Q [19].

References