TY  - JOUR
AB  - 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.
AU  - Detzner, Johanna
AU  - Krojnewski, Elisabeth
AU  - Pohlentz, Gottfried
AU  - Steil, Daniel
AU  - Humpf, Hans-Ulrich
AU  - Mellmann, Alexander
AU  - Karch, Helge
AU  - Müthing, Johannes
DA  - 2021-02-12
DO  - 10.17879/72089628015
KW  - pHRCEpiCs
KW  - EHEC
KW  - kidney cortical epithelial cells
KW  - glycolipids
KW  - receptor
KW  - Shiga toxin
KW  - Stx1a
KW  - Stx2a
KW  - STEC
LA  - eng
N1  - Toxins 13 (2021) 2, 139, 1-24
N1  - Finanziert durch den Open-Access-Publikationsfonds der Westfälischen Wilhelms-Universität Münster (WWU Münster).
N1  - Förderer: German Center for Infection Research / Projektnummer: 06.801
N1  - Funding organisation: German Center for Infection Research / Project number: 06.801
N1  - Förderer: German Center for Infection Research / Projektnummer: 03ZZ0805B
N1  - Funding organisation: German Center for Infection Research / Project number: 03ZZ0805B
PY  - 2021-02-12
TI  - Shiga Toxin (Stx)-Binding Glycosphingolipids of Primary Human Renal Cortical Epithelial Cells (pHRCEpiCs) and Stx-Mediated Cytotoxicity
UR  - https://nbn-resolving.org/urn:nbn:de:hbz:6-02059524824
Y2  - 2024-11-22T03:24:58
ER  -