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. 2020 Apr 28;10:7157. doi: 10.1038/s41598-020-64040-1

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© The Author(s) 2020

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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(A) Data presented in Fig. 1D were re-analyzed to visualize a significant N-Myc-mediated effect on glutathione (GSH) metabolism. In total, 32 out of 34 GSH-related metabolites are significantly affected by N-Myc levels according to ANOVA. (B) Main routes of the glutathione pathway (modified from³⁰). Metabolites which are significantly affected by N-Myc for the sample groups under constant glucose and varying glutamine concentration in the medium are marked by red boxes. Interestingly, all significantly altered species are found to be decreased upon MYCN induction. Metabolites that have not been detected by UPLC are greyed (AA: amino acid, BCKA: branched chain keto acids, F-6-P: fructose-6-phosphate, GSSG: glutathione disulfide, LOOH: lipid hydroxyperoxide, LOH: lipid peroxyl radical, NA-cysteine: N-acetyl-cysteine, OTC: oxothiazolidine-4-carboxylate, R-5-P: ribose-5-phosphate, R, R*: radicals, X: xenobiotic). (C,D) Redox modulation by addition of GSH (100 mM) in the presence of varying concentrations of DON (C) or the ROS-inducer mono-methyl fumarate (MMF, D) in SHEP-TR-MYCN cells with or without induction of MYCN expression (“+Tet” and “−Tet”, respectively).