Free Sphingoid Bases

Norred, W. P., Plattner, R. D., Meredith, F. I., and Riley, R. T. (1997). Mycotoxin-induced elevation of free sphingoid bases in precision-cut rat liver slices Specificity of the response and structure-activity relationships. Toxicol. Appl. Pharmacol. 147, 63-70. 

Olivera, A., Rosenthal, J., Spiegel, S. Sphingosine kinase from Swiss 3T3 fibroblasts a convenient assay for the measurement of intracellular levels of free sphingoid bases. Anal Biochem 223 (1994) 306-312. 

In lysosomes, Cers are hydrolyzed to free sphingoid bases and long-chain fatty acids by a ceramidase that has an acidic pH optimum. The lysosomal ceramidase is a water-soluble glycoprotein that hydrolyzes membrane-bound Cer in an interfacial reaction that requires stimulation by SAP-C or SAP-D and anionic phospholipids such as BMP (A. Klein, 1994 T. Linke, 2(X)1). The human acidic ceramidase is a heterodimer of 40-kDa and 13-kDa subunits synthesized as a single precursor polypeptide and is targeted to the lysosome via the mannose 6-phosphate receptor (K. Ferlinz, 2001). 

Additional information <1, 6> (<1,6> simple quantitative radio-assay [1] <1> assay for measurement of intracellular levels of free sphingoid bases [22]) [1, 15, 22]... 

Sphingosine and sphingosine 1-phosphate can induce DNA synthesis in growth-arrested Swiss 3T3 cells. FBj incubated with the cells elevated sphingosine and induced an increase in [ H] thymidine incorporation into DNA (59). Further studies showed that sphinganine was required for stimulation of DNA synthesis. Studies with LLC-PK renal cells showed a close correlation between fumonisin-induced cytotoxicity and inhibition of de novo sphingolipid biosyntheses (82). However, studies with primary rat hepatocytes have not shown any relationship between cytotoxicity and elevation of free sphingoid bases (38). 

Our work has focused on confirmation of a similar mode of action in plant tissues (10). Following treatment with FBj or AAL-toxin, the free sphingoid bases, phytosphingos-ine and sphinganine, were found to be markedly elevated relative to controls in the duckweed bioassay (Table 2). Extracts of treated tomato plants and tobacco callus cultures showed the same results. FBj and AAL-toxin caused 18- and 45-fold increases in phytosphingosine and 76- and 129-fold increases in sphinganine, respectively, after 24 h (10). 

Phytosphingosine and sphingosine also have phytotoxic effects on duckweed at higher concentrations (50 pM) causing increased conductivity and chlorophyll loss (75). This suggests that the build-up of free sphingoid bases is toxic to cells (65, 75). The... 

It is unknown how the elevated levels of free sphingoid bases caused by FB and AAL-toxin in plants might mediate the physiological changes observed. It is possible that changes in membrane permeability are involved. The structural analogy with sphingosine... 

Lavie,Y, Blusztain, J.K., Liscovitch, M., 1994, Formation of endogenous free sphingoid bases in cells induced by changing medium conditions, Biochim.Biophys.Acta. 1220(3) 323-328. 

Wakita, H., Nishimura, K., and Takigawa, M., Composition of free long-chain (sphingoid) bases in stratum corneum of normal and pathologic human skin conditions, J. Invest. Dermatol., 99, 617,... 

The TMS ethers of the base with a free amine group have also been employed for GC-MS [461]. Again there is no molecular ion, although the molecular weight is indicated by an ion equivalent to [M-15f, and there are prominent fragments for cleavage between carbons 1 and 2 and between carbons 2 and 3. The structures of several natural sphingoid... 

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