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| 001 | 124296 | ||
| 005 | 20240228145505.0 | ||
| 024 | 7 | _ | |a 10.1194/jlr.D076190 |2 doi |
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| 024 | 7 | _ | |a 0022-2275 |2 ISSN |
| 024 | 7 | _ | |a 1539-7262 |2 ISSN |
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| 037 | _ | _ | |a DKFZ-2017-01192 |
| 041 | _ | _ | |a eng |
| 082 | _ | _ | |a 540 |
| 100 | 1 | _ | |a von Gerichten, Johanna |0 0000-0002-9224-5296 |b 0 |e First author |
| 245 | _ | _ | |a Diastereomer-specific quantification of bioactive hexosylceramides from bacteria and mammals. |
| 260 | _ | _ | |a Bethesda, Md. |c 2017 |b ASBMB |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1511258639_9860 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
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| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a Mammals synthesize, cell-type specifically, the diastereomeric hexosylceramides, β-galactosylceramide (GalCer) and β-glucosylceramide (GlcCer), which are involved in several diseases, such as sphingolipidosis, diabetes, chronic kidney diseases, or cancer. In contrast, Bacteroides fragilis, a member of the human gut microbiome, and the marine sponge, Agelas mauritianus, produce α-GalCer, one of the most potent stimulators for invariant natural killer T cells. To dissect the contribution of these individual stereoisomers to pathologies, we established a novel hydrophilic interaction chromatography-based LC-MS(2) method and separated (R > 1.5) corresponding diastereomers from each other, independent of their lipid anchors. Testing various bacterial and mammalian samples, we could separate, identify (including the lipid anchor composition), and quantify endogenous β-GlcCer, β-GalCer, and α-GalCer isomers without additional derivatization steps. Thereby, we show a selective decrease of β-GlcCers versus β-GalCers in cell-specific models of GlcCer synthase-deficiency and an increase of specific β-GlcCers due to loss of β-glucoceramidase 2 activity. Vice versa, β-GalCer increased specifically when cerebroside sulfotransferase (Gal3st1) was deleted. We further confirm β-GalCer as substrate of globotriaosylceramide synthase for galabiaosylceramide synthesis and identify additional members of the human gut microbiome to contain immunogenic α-GalCers. Finally, this method is shown to separate corresponding hexosylsphingosine standards, promoting its applicability in further investigations. |
| 536 | _ | _ | |a 317 - Translational cancer research (POF3-317) |0 G:(DE-HGF)POF3-317 |c POF3-317 |f POF III |x 0 |
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| 700 | 1 | _ | |a Schlosser, Kerstin |b 1 |
| 700 | 1 | _ | |a Lamprecht, Dominic |0 P:(DE-He78)9b090037531356fc2cc46d832af8c7a6 |b 2 |u dkfz |
| 700 | 1 | _ | |a Morace, Ivan |0 P:(DE-He78)4440e062d913fde6de3ddc4d2466fad8 |b 3 |u dkfz |
| 700 | 1 | _ | |a Eckhardt, Matthias |b 4 |
| 700 | 1 | _ | |a Wachten, Dagmar |0 0000-0003-4800-6332 |b 5 |
| 700 | 1 | _ | |a Jennemann, Richard |0 P:(DE-He78)3caae9893e3b2704f7bb5a9646ef084d |b 6 |u dkfz |
| 700 | 1 | _ | |a Gröne, Hermann-Josef |0 0000-0003-3613-2649 |b 7 |
| 700 | 1 | _ | |a Mack, Matthias |0 0000-0002-7753-2422 |b 8 |
| 700 | 1 | _ | |a Sandhoff, Roger |0 P:(DE-He78)a928ded2085c8911822370cad0b4a728 |b 9 |e Last author |u dkfz |
| 773 | _ | _ | |a 10.1194/jlr.D076190 |g Vol. 58, no. 6, p. 1247 - 1258 |0 PERI:(DE-600)1466675-3 |n 6 |p 1247 - 1258 |t Journal of lipid research |v 58 |y 2017 |x 1539-7262 |
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