scholarly journals Human fibroblasts in culture metabolize differently exogenous G(M3) ganglioside species containing C18 and C20 sphingosine.

1998 ◽  
Vol 45 (2) ◽  
pp. 385-392
Author(s):  
V Chigorno ◽  
M Valsecchi ◽  
S Sonnino
Keyword(s):  
Human Fibroblasts ◽  
Decisive Role ◽  
Metabolic Fate ◽  
Base Content ◽  
Long Chain Base ◽  
Complex Lipids ◽  
Sphingolipid Biosynthesis ◽  
Ganglioside Species ◽  
Long Chain ◽  
Complex Sphingolipids

Preparation of radioactive GM3 species containing isotopically labeled C18 sphingosine or C20 sphingosine is reported and their use for studying some aspects of the sphingolipid biosynthesis in cells is discussed. Human fibroblasts in culture that have only C18 sphingolipids and GM3 as the major gangliosides, were fed with the two radioactive GM3 species. The radioactive gangliosides were taken up by the cells and metabolized. The analyses of the radioactivity metabolic fate, in this model provides the following information. i--About 70-80% of the total catabolic sphingosine is re-cycled for biosynthesis of complex sphingolipids. ii--A small amount of the catabolic C20 sphingosine was re-cycled for biosynthesis of C20 sphingolipids, thus yielding complex lipids that are not naturally present in fibroblast cells. iii--A regulatory step in the biosynthesis of sphingolipid species differring long chain base content, C18 or C20 sphingosine, is in some way involved in the first steps of sphingolipid biosynthesis, and thus plays a decisive role in the availability of the long chain bases.

scholarly journals Different metabolic recycling of the lipid components of exogenous sulphatide in human fibroblasts

1988 ◽  
Vol 252 (2) ◽  
pp. 375-379 ◽  
Author(s):  
M Trinchera ◽  
U Wiesmann ◽  
M Pitto ◽  
D Acquotti ◽  
R Ghidoni
Keyword(s):  
Fatty Acid ◽  
Human Fibroblasts ◽  
Total Lipid Extract ◽  
Phospholipid Biosynthesis ◽  
Metabolic Fate ◽  
Long Chain Base ◽  
Cultured Human Fibroblasts ◽  
Almost All ◽  
Long Chain ◽  
Ceramide Moiety

Cultured human fibroblasts were fed with two differently labelled sulphatide molecules [one labelled on C-3 of the sphingosine (Sph) moiety [(Sph-3H]sulphatide), the second on C-1 of stearic acid [(stearoyl-14C]sulphatide)], and the intracellular metabolic fate of radioactivity was monitored. Incorporated radioactivity was almost all recovered in the total lipid extract, regardless of the labelling position of the added sulphatide; however, large differences in the level of incorporation occurred among labelled glycosphingolipids. For example, sphingomyelin was present as the major radiolabelled lipid after [Sph-3H]-sulphatide incubation, but was detectable only in trace amounts after [stearoyl-14C]sulphatide administration; in the latter case the radioactivity was located predominantly in glycerophospholipids. From this finding it can be inferred that the free long-chain base (sphingosine) that originates from lysosomal catabolism of sulphatide is mainly, and quite specifically, utilized for sphingomyelin biosynthesis, whereas the ceramide moiety is not; conversely the fatty acid released from ceramide is non-specifically re-utilized for phospholipid biosynthesis.

scholarly journals Rescue of cell growth by sphingosine with disruption of lipid microdomain formation in Saccharomyces cerevisiae deficient in sphingolipid biosynthesis

2006 ◽  
Vol 394 (1) ◽  
pp. 237-242 ◽  
Author(s):  
Motohiro Tani ◽  
Akio Kihara ◽  
Yasuyuki Igarashi
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Growth ◽  
Serine Palmitoyltransferase ◽  
Kinase Gene ◽  
Yeast Saccharomyces Cerevisiae ◽  
Long Chain Base ◽  
Triton X ◽  
Lipid Microdomain ◽  
Sphingolipid Biosynthesis ◽  
Complex Sphingolipids

In the yeast Saccharomyces cerevisiae, sphingolipids are essential for cell growth. Inactivation of sphingolipid biosynthesis, such as by disrupting the serine palmitoyltransferase gene (LCB2), is lethal, but cells can be rescued by supplying an exogenous LCB (long-chain base) like PHS (phytosphingosine) or DHS (dihydrosphingosine). In the present study, supplying SPH (sphingosine), an unnatural LCB for yeast, similarly rescued the Δlcb2 cells, but only when SPH 1-phosphate production was inhibited by deleting the LCB kinase gene LCB4. Exogenously added SPH was adequately converted into phosphoinositol-containing complex sphingolipids. Interestingly, cells carrying SPH-based sphingolipids exhibited a defect in the association of Pma1p with Triton X-100-insoluble membrane fractions, and displayed sensitivities to both Ca2+ and hygromycin B. These results suggest that the SPH-based sphingolipids in these cells have properties that differ from those of the PHS- or DHS-based sphingolipids in regard to lipid microdomain formation, leading to abnormal sensitivities towards certain environmental stresses. The present paper is the first report showing that in sphingolipid-deficient S. cerevisiae, the requirement for LCB can be fulfilled by exogenous SPH, although this supplement results in failure of lipid microdomain formation.

scholarly journals Sphingolipids Mediate Differential Echinocandin Susceptibility in Candida albicans and Aspergillus nidulans

2015 ◽  
Vol 59 (6) ◽  
pp. 3377-3384 ◽  
Author(s):  
Kelley R. Healey ◽  
Krishna K. Challa ◽  
Thomas D. Edlind ◽  
Santosh K. Katiyar
Keyword(s):  
Candida Albicans ◽  
Aspergillus Nidulans ◽  
Laboratory Strain ◽  
Wild Type ◽  
Enoyl Reductase ◽  
Content Type ◽  
Long Chain Base ◽  
Membrane Target ◽  
Sphingolipid Biosynthesis ◽  
Long Chain

ABSTRACTThe cell wall synthesis-inhibiting echinocandins, including caspofungin and micafungin, play important roles in the treatment of candidiasis and aspergillosis. Previous studies revealed that, in the haploid yeastCandida glabrata, sphingolipid biosynthesis pathway mutations confer caspofungin reduced susceptibility (CRS) but micafungin increased susceptibility (MIS). Here, we describe oneCandida albicansstrain (of 10 tested) that similarly yields CRS-MIS mutants at relatively high frequency. Mutants demonstrated increased levels of long-chain bases (sphingolipid pathway intermediates) and, unique to this strain, loss of His104/Pro104 heterozygosity in theTSC13-encoded enoyl reductase. CRS-MIS was similarly observed in aC. albicanshomozygousfen1Δfen12Δ laboratory strain and in diverse wild-type strains following exogenous long-chain-base treatment. Analogous to these results, CRS-MIS was demonstrated in anAspergillus nidulansbasAmutant encoding defective sphingolipid C4-hydroxylase and in its wild-type parent exposed to long-chain bases. Sphingolipids likely modulate echinocandin interaction with their Fks membrane target in all susceptible fungi, with potential implications for optimizing therapy with existing antifungals and the development of novel agents.

scholarly journals The protein kinase Sch9 is a key regulator of sphingolipid metabolism in Saccharomyces cerevisiae

2014 ◽  
Vol 25 (1) ◽  
pp. 196-211 ◽  
Author(s):  
Erwin Swinnen ◽  
Tobias Wilms ◽  
Jolanta Idkowiak-Baldys ◽  
Bart Smets ◽  
Pepijn De Snijder ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Protein Kinase ◽  
Yeast Cells ◽  
Sphingolipid Metabolism ◽  
Long Chain Base ◽  
Aureobasidin A ◽  
Long Chain ◽  
Complex Sphingolipids

The Saccharomyces cerevisiae protein kinase Sch9 is an in vitro and in vivo effector of sphingolipid signaling. This study examines the link between Sch9 and sphingolipid metabolism in S. cerevisiae in vivo based on the observation that the sch9Δ mutant displays altered sensitivity to different inhibitors of sphingolipid metabolism, namely myriocin and aureobasidin A. Sphingolipid profiling indicates that sch9Δ cells have increased levels of long-chain bases and long-chain base-1 phosphates, decreased levels of several species of (phyto)ceramides, and altered ratios of complex sphingolipids. We show that the target of rapamycin complex 1–Sch9 signaling pathway functions to repress the expression of the ceramidase genes YDC1 and YPC1, thereby revealing, for the first time in yeast, a nutrient-dependent transcriptional mechanism involved in the regulation of sphingolipid metabolism. In addition, we establish that Sch9 affects the activity of the inositol phosphosphingolipid phospholipase C, Isc1, which is required for ceramide production by hydrolysis of complex sphingolipids. Given that sphingolipid metabolites play a crucial role in the regulation of stress tolerance and longevity of yeast cells, our data provide a model in which Sch9 regulates the latter phenotypes by acting not only as an effector but also as a regulator of sphingolipid metabolism.

scholarly journals Cyclic AMP accumulation in HeLa cells induced by cholera toxin. Involvement of the ceramide moiety of GM1 ganglioside

1990 ◽  
Vol 271 (1) ◽  
pp. 107-111 ◽  
Author(s):  
M Masserini ◽  
P Palestini ◽  
M Pitto ◽  
V Chigorno ◽  
M Tomasi ◽  
...  
Keyword(s):  
Cyclic Amp ◽  
Cholera Toxin ◽  
Molecular Species ◽  
Hela Cells ◽  
Gm1 Ganglioside ◽  
Cyclic Amp Accumulation ◽  
Long Chain Base ◽  
Ganglioside Species ◽  
Long Chain ◽  
Ceramide Moiety

The influence of ceramide composition on the rate of GM1 association to HeLa cells has been investigated by incubating the cells in the presence of either native ganglioside or molecular species carrying highly homogeneous long chain base moieties, fractionated from native GM1. The GM1 ganglioside species carrying the unsaturated C18 long chain base moiety proved to have the fastest rate of association, whereas the saturated species carrying 20 carbon atoms had the slowest rate. After having increased the GM1 cell content (65-fold) by incubation with the various ganglioside species, the cells were incubated with cholera toxin and the time course of cyclic AMP accumulation was monitored. Remarkable differences among cells enriched with the various molecular species were found in the duration of the lag time preceding the accumulation of cyclic AMP, the shortest being displayed by the unsaturated C18 species. Moreover, the amount of cyclic AMP accumulated after a given time of incubation with cholera toxin was significantly higher when the C18:1-GM1 species was present than with native GM1. Fluorescence anisotropy experiments, carried out using the probe 1,3-diphenylhexatriene, show that the GM1 ganglioside ceramide moiety was also modifying the cell membrane fluidity of the host.

scholarly journals Sphingolipids of Asteroidea and Holothuroidea: Structures and Biological Activities

Marine Drugs ◽  
2021 ◽  
Vol 19 (6) ◽  
pp. 330
Author(s):  
Timofey V. Malyarenko ◽  
Alla A. Kicha ◽  
Valentin A. Stonik ◽  
Natalia V. Ivanchina
Keyword(s):  
Marine Invertebrates ◽  
Biological Activities ◽  
Complete Information ◽  
Structural Features ◽  
Marine Organisms ◽  
Structural Components ◽  
Chemical Structures ◽  
The Past ◽  
Complex Lipids ◽  
Complex Sphingolipids

Sphingolipids are complex lipids widespread in nature as structural components of biomembranes. Commonly, the sphingolipids of marine organisms differ from those of terrestrial animals and plants. The gangliosides are the most complex sphingolipids characteristic of vertebrates that have been found in only the Echinodermata (echinoderms) phylum of invertebrates. Sphingolipids of the representatives of the Asteroidea and Holothuroidea classes are the most studied among all echinoderms. In this review, we have summarized the data on sphingolipids of these two classes of marine invertebrates over the past two decades. Recently established structures, properties, and peculiarities of biogenesis of ceramides, cerebrosides, and gangliosides from starfishes and holothurians are discussed. The purpose of this review is to provide the most complete information on the chemical structures, structural features, and biological activities of sphingolipids of the Asteroidea and Holothuroidea classes.

scholarly journals Long-chain base phosphates modulate pollen tube growth via channel-mediated influx of calcium

2014 ◽  
Vol 79 (3) ◽  
pp. 507-516 ◽  
Author(s):  
Juyou Wu ◽  
Xiaoya Qin ◽  
Shutian Tao ◽  
Xueting Jiang ◽  
Yun-Kuan Liang ◽  
...  
Keyword(s):  
Pollen Tube ◽  
Pollen Tube Growth ◽  
Tube Growth ◽  
Chain Base ◽  
Long Chain Base ◽  
Long Chain
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