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Metabolomic analysis of Shiga toxin 2a-induced injury in conditionally immortalized glomerular endothelial cells

IntroductionShiga toxin 2a (Stx2a) induces hemolytic uremic syndrome (STEC HUS) by targeting glomerular endothelial cells (GEC).ObjectivesWe investigated in a metabolomic analysis the response of a conditionally immortalized, stable glomerular endothelial cell line (ciGEnC) to Stx2a stimulation as a...

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Main Authors: Patry, Christian (Author) , Betzen, Christian (Author) , Perez Ortiz, Alba (Author) , Tönshoff, Burkhard (Author) , Rafat, Neysan (Author)
Format: Article (Journal)
Language:English
Published: 01 October 2019
In: Metabolomics
Year: 2019, Volume: 15, Issue: 10
ISSN:1573-3890
DOI:10.1007/s11306-019-1594-2
Online Access:Verlag, Volltext: https://doi.org/10.1007/s11306-019-1594-2
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Author Notes:Christian Patry, Kathrin Plotnicki, Christian Betzen, Alba Perez Ortiz, Kirk L. Pappan, Simon C. Satchell, Peter W. Mathieson, Martina Bielaszewska, Helge Karch, Burkhard Tönshoff, Neysan Rafat
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Summary:IntroductionShiga toxin 2a (Stx2a) induces hemolytic uremic syndrome (STEC HUS) by targeting glomerular endothelial cells (GEC).ObjectivesWe investigated in a metabolomic analysis the response of a conditionally immortalized, stable glomerular endothelial cell line (ciGEnC) to Stx2a stimulation as a cell culture model for STEC HUS.MethodsCiGEnC were treated with tumor necrosis factor-(TNF)α, Stx2a or sequentially with TNFα and Stx2a. We performed a metabolomic high-throughput screening by lipid- or gas chromatography and subsequent mass spectrometry. Metabolite fold changes in stimulated ciGEnC compared to untreated cells were calculated.Results320 metabolites were identified and investigated. In response to TNFα + Stx2a, there was a predominant increase in intracellular free fatty acids and amino acids. Furthermore, lipid- and protein derived pro-inflammatory mediators, oxidative stress and an augmented intracellular energy turnover were increased in ciGEnC. Levels of most biochemicals related to carbohydrate metabolism remained unchanged.ConclusionStimulation of ciGEnC with TNFα + Stx2a is associated with profound metabolic changes indicative of increased inflammation, oxidative stress and energy turnover.
Item Description:Gesehen am 29.10.2019
Physical Description:Online Resource
ISSN:1573-3890
DOI:10.1007/s11306-019-1594-2

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