Diastereomer-specific quantification of bioactive hexosylceramides from bacteria and mammals[S]
Diastereomer-specific quantification of bioactive hexosylceramides from bacteria and mammals[S]
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细菌和哺乳动物生物活性己糖神经酰胺的非对映体特异性定量[S]
DOI：
10.1194/jlr.d076190
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发表时间：
2017
影响因子：
6.5
通讯作者：
R. Sandhoff
中科院分区：
文献类型：
--
作者：
J. von Gerichten;Kerstin Schlosser;Dominic Lamprecht;Ivan Morace;M. Eckhardt;D. Wachten;R. Jennemann;H. Gröne;M. Mack;R. Sandhoff
哺乳动物合成（细胞类型特异性地）非对映异构的己糖神经酰胺、β-半乳糖神经酰胺（GalCer）和β-葡糖神经酰胺（GlcCer），其涉及几种疾病，例如鞘脂病、糖尿病、慢性肾病或癌症。相比之下，脆弱拟杆菌（Bacteroides fragilis）是人类肠道微生物组的成员，而海绵Agelas mauritianus则产生α-GalCer，这是不变自然杀伤T细胞最有效的刺激物之一。为了剖析这些单独的立体异构体对病理学的贡献，我们建立了一种新型的基于亲水相互作用色谱的LC-MS 2方法，并独立于其脂质锚定物而相互分离（R > 1.5）相应的非对映体。测试各种细菌和哺乳动物样品，我们可以分离、鉴定（包括脂质锚组成）和定量内源性β-GlcCer、β-GalCer和α-GalCer异构体，而无需额外的衍生化步骤。因此，我们在GlcCer β-葡萄糖酰胺酶缺乏的细胞特异性模型中显示β-GlcCer相对于β-GalCer的选择性减少，并且由于β-葡萄糖角蛋白酰胺酶2活性的丧失，特异性β-GlcCer增加。反之亦然，β-GalCer增加，特别是当β-半乳糖苷磺基转移酶（Gal 3st 1）删除。我们进一步证实β-GalCer是用于半乳糖苷神经酰胺合成的globotriaosylceramide合酶的底物，并鉴定了含有免疫原性α-GalCer的人肠道微生物组的其他成员。最后，这种方法被证明是分离相应的己糖鞘氨醇标准品，促进其适用性在进一步的调查。
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-MS2 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.
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葡萄糖神经酰胺增加的 β-葡萄糖苷酶 2 敲除小鼠表现出肝再生受损
影响因子：
6.7
作者：
Gonzalez-Carmona MA;Sandhoff R;Tacke F;Vogt A;Weber S;Canbay AE
通讯作者：
Canbay AE
影响因子：
32.4
作者：
Kain, Lisa;Webb, Bill;Anderson, Brian L.;Deng, Shenglou;Holt, Marie;Costanzo, Anne;Zhao, Meng;Self, Kevin;Teyton, Anais;Everett, Chris;Kronenberg, Mitchell;Zajonc, Dirk M.;Bendelac, Albert;Savage, Paul B.;Teyton, Luc
通讯作者：
Teyton, Luc
DOI：
10.1073/pnas.1217775110
发表时间：
2013
期刊：
Proceedings of the National Academy of Sciences
影响因子：
--
作者：
Stettner P;Bourgeois S;Marsching C;Traykova-Brauch M;Porubsky S;Nordstrom V;Hopf C;Koesters R;Sandhoff R;Wiegandt H;Wagner CA;Grone HJ;Jennemann R
通讯作者：
Jennemann R
影响因子：
4.1
作者：
Eckhardt, M;Yaghootfam, A;Gieselmann, V
通讯作者：
Gieselmann, V
影响因子：
32.4
作者：
Darmoise A;Teneberg S;Bouzonville L;Brady RO;Beck M;Kaufmann SH;Winau F
通讯作者：
Winau F