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PubMedDate not supplied

Anticancer compounds and sphingolipid metabolism in the colon.

Sphingomyelin metabolism generates anticancer signals such as ceramide and sphingosine that may inhibit cell proliferation, and induce differentiation and apoptosis. Changes of sphingomyelin metabolism are found to be associated with tumorigenesis in various tissues and a particular link between sphingomyelin metabolism and colon cancer has been indicated. The effects of several anticancer drugs on sphingomyelin metabolism have been examined recently and there is an increasing interest in discovering new drugs taking sphingomyelin as a target. The present review outlines the sphingomyelin metabolism pathway, introduces the evidence linking sphingomyelin to colon cancer, and summarizes the anticancer drugs and dietary factors that affect the metabolism of sphingomyelin and, thus, the production of the anticancer messengers in the colon.

Animals↗
PubMed2005

[Molecular targeting therapy for leukemia by sphingolipid ceramide].

Ceramide has been recognized as a structural component to consist of the cell membrane. Since we reported that ceramide content increased in vitamin-D3-induced cell differentiation of human leukemia HL-60 cells, it has become evident that ceramide acts as an intracellular lipid mediator to transduce an extracellular stress into the cells. Ceramide is synthesized through serine-palmitoyl CoA transferase. Diversity of ceramide species derives from the changes of carbon length of fatty acid binding to amine part of sphingosine. A variety of stresses induce apoptosis through activation of pro-apoptotic signals as well as inhibition of antiapoptotic/survival signals by an increase of intracellular ceramide. Here, the recent problems and innovation in the medication of hematological malignancy are summarized, and it is suggested that the induction of apoptotic cell death by ceramide action is a potent, novel molecular targeting therapy for a chemoresistant and refractory hematological malignancy.

Apoptosis↗
PubMed1976

Sphingolipid base metabolism. Partial purification and properties of sphinganine kinase of brain.

The presence of sphinganine kinase in bovine brain has been demonstrated. The product of the action of the brain enzyme on sphinganine has been characterized as sphingamine 1-phosphate by a combination of chemical, enzymatic, and chromatographic techniques. The bovine brain enzyme has been partially purified and appears to exist in multiple forms. The molecular weight of the most highly purified preparation of the enzyme was estimated to be 190,000 by gel filtration. The purified form of the enzyme showed highest activity with ATP but was also active with other purine nucleoside triphosphates. UTP and CTP did not serve as substrates for the enzyme.

Animals↗
PubMed1989

Modulation of phosphorylase kinase activity by sphingolipids.

Psychosine (galactosyl sphingosine) potently inhibits the activity of both nonactivated and activated by covalent modification (autophosphorylation and limited proteolysis) rabbit skeletal muscle phosphorylase kinase. Half-maximal inhibition was observed at 44 microM or 66 microM when the kinase activity was assayed at pH 6.8 or 8.2 respectively. Sphingosine was also inhibitory, but only at pH 6.8 (half-maximal inhibition was observed at 130 microM). In this respect, sphingomyelin, cerebroside and cerebroside sulfate were ineffective. On the other hand, a number of gangliosides stimulated the activity of nonactivated phosphorylase kinase at neutral pH. Among the individual gangliosides tested the activation potency was GD1a greater than GT1b greater than GM1, while GM3 was without effect. Most important, GD1a dramatically increases the activity of the kinase at low Ca2+ concentrations. Both psychosine and GD1a increased the rate of kinase autophosphorylation on alpha- subunit only, but although ganglioside-induced stimulation of autophosphorylation was accompanied with an enhancement of the rate of autoactivation at pH 6.8, psychosine completely blocked autoactivation.

Animals↗
PubMed1974

Stimulation of erythroblast maturation in vitro by sphingolipids.

A lipid factor previously isolated from leukocytes and found to stimulate basophilic erythroblast formation in an in vitro system of incubated rabbit bone marrow cells has been analyzed by thin-layer chromatography, gas-liquid chromatography, and gas-liquid chromatography-mass spectrometry. The biologically active components are sphingosine ceramides of tetracosanoic and dehydrotetracosanoic acids. Tests of a series of related ceramides show a high degree of structural specificity for the C(24)-V-acyl compounds with significant but markedly lower activity of the C(22) analog. Commercially available sphingomyelin shows activity comparable to that of the tetracosanoic acid ceramide. Sphingosine and tetracosanic acid supplied in equimolar amounts have negligible activity. The results, in the context of other findings, suggest a possible supportive role of plasma ceramides and sphingomyelins in red cell maturation.

Animals↗