Shiga Toxin (Stx)-Binding Glycosphingolipids of Primary Human Renal Cortical Epithelial Cells (pHRCEpiCs) and Stx-Mediated Cytotoxicity
Human kidney epithelial cells are supposed to be directly involved in the pathogenesis of the hemolytic–uremic syndrome (HUS) caused by Shiga toxin (Stx)-producing enterohemorrhagic Escherichia coli (EHEC). The characterization of the major and minor Stx-binding glycosphingolipids (GSLs) globotriaos...
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FB/Einrichtung: | FB 05: Medizinische Fakultät |
Dokumenttypen: | Artikel |
Medientypen: | Text |
Erscheinungsdatum: | 2021 |
Publikation in MIAMI: | 13.10.2022 |
Datum der letzten Änderung: | 13.10.2022 |
Angaben zur Ausgabe: | [Electronic ed.] |
Quelle: | Toxins 13 (2021) 2, 139, 1-24 |
Schlagwörter: | pHRCEpiCs; EHEC; kidney cortical epithelial cells; glycolipids; receptor; Shiga toxin; Stx1a; Stx2a; STEC |
Fachgebiet (DDC): | 610: Medizin und Gesundheit |
Lizenz: | CC BY 4.0 |
Sprache: | English |
Förderung: | Finanziert durch den Open-Access-Publikationsfonds der Westfälischen Wilhelms-Universität Münster (WWU Münster). Förderer: German Center for Infection Research / Projektnummer: 06.801 Förderer: German Center for Infection Research / Projektnummer: 03ZZ0805B |
Format: | PDF-Dokument |
URN: | urn:nbn:de:hbz:6-02059524824 |
Weitere Identifikatoren: | DOI: 10.17879/72089628015 |
Permalink: | https://nbn-resolving.de/urn:nbn:de:hbz:6-02059524824 |
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Onlinezugriff: | 10.3390_toxins13020139.pdf |
Human kidney epithelial cells are supposed to be directly involved in the pathogenesis of the hemolytic–uremic syndrome (HUS) caused by Shiga toxin (Stx)-producing enterohemorrhagic Escherichia coli (EHEC). The characterization of the major and minor Stx-binding glycosphingolipids (GSLs) globotriaosylceramide (Gb3Cer) and globotetraosylceramide (Gb4Cer), respectively, of primary human renal cortical epithelial cells (pHRCEpiCs) revealed GSLs with Cer (d18:1, C16:0), Cer (d18:1, C22:0), and Cer (d18:1, C24:1/C24:0) as the dominant lipoforms. Using detergent-resistant membranes (DRMs) and non-DRMs, Gb3Cer and Gb4Cer prevailed in the DRM fractions, suggesting their association with microdomains in the liquid-ordered membrane phase. A preference of Gb3Cer and Gb4Cer endowed with C24:0 fatty acid accompanied by minor monounsaturated C24:1-harboring counterparts was observed in DRMs, whereas the C24:1 fatty acid increased in relation to the saturated equivalents in non-DRMs. A shift of the dominant phospholipid phosphatidylcholine with saturated fatty acids in the DRM to unsaturated species in the non-DRM fractions correlated with the GSL distribution. Cytotoxicity assays gave a moderate susceptibility of pHRCEpiCs to the Stx1a and Stx2a subtypes when compared to highly sensitive Vero-B4 cells. The results indicate that presence of Stx-binding GSLs per se and preferred occurrence in microdomains do not necessarily lead to a high cellular susceptibility towards Stx.