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

Autor: Patry C; Department of Pediatrics I, University Children's Hospital Heidelberg, 69120, Heidelberg, Germany.; Division of Cardiovascular Physiology, Institute of Physiology and Pathophysiology, University of Heidelberg, 69120, Heidelberg, Germany., Plotnicki K; Department of Pediatrics I, University Children's Hospital Heidelberg, 69120, Heidelberg, Germany., Betzen C; Department of Pediatrics I, University Children's Hospital Heidelberg, 69120, Heidelberg, Germany.; Division of Functional Genome Analysis, German Cancer Research Center (DKFZ), 69120, Heidelberg, Germany., Ortiz AP; Department of Neonatology, University Children's Hospital Mannheim, University of Heidelberg, 68167, Mannheim, Germany., Pappan KL; Metabolon, Inc., 617 Davis Drive, Suite 400, Durham, NC, 27713, USA., Satchell SC; Learning and Research Southmead Hospital Bristol, University of Bristol, Bristol, BS8 1TH, UK., Mathieson PW; The Principal's Office, University of Edinburgh, Edinburgh, EH8 9YL, UK., Bielaszewska M; Institute for Hygiene, University of Münster, 48149, Münster, Germany.; Reference Laboratory for E. coli and Shigella, National Public Health Institute, Srobarova 48, 10042, Prague, Czech Republic., Karch H; Institute for Hygiene, University of Münster, 48149, Münster, Germany., Tönshoff B; Department of Pediatrics I, University Children's Hospital Heidelberg, 69120, Heidelberg, Germany., Rafat N; Department of Pediatrics I, University Children's Hospital Heidelberg, 69120, Heidelberg, Germany. Neysan.Rafat@umm.de.; Department of Neonatology, University Children's Hospital Mannheim, University of Heidelberg, 68167, Mannheim, Germany. Neysan.Rafat@umm.de.; Department of Pharmaceutical Sciences, Bahá'í Institute of Higher Education (BIHE), Teheran, Iran. Neysan.Rafat@umm.de.
Jazyk: angličtina
Zdroj: Metabolomics : Official journal of the Metabolomic Society [Metabolomics] 2019 Oct 01; Vol. 15 (10), pp. 131. Date of Electronic Publication: 2019 Oct 01.
DOI: 10.1007/s11306-019-1594-2
Abstrakt: Introduction: Shiga toxin 2a (Stx2a) induces hemolytic uremic syndrome (STEC HUS) by targeting glomerular endothelial cells (GEC).
Objectives: We 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.
Methods: CiGEnC 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.
Results: 320 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.
Conclusion: Stimulation of ciGEnC with TNFα + Stx2a is associated with profound metabolic changes indicative of increased inflammation, oxidative stress and energy turnover.
Databáze: MEDLINE
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