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Bernd Kammerer  - - - 
Top co-authors See all
Manfred Jung

256 shared publications

Institute of Pharmaceutical Sciences, University of Freiburg, Albertstraße 25, 79104 Freiburg im Breisgau, Germany

Andreas Zell

142 shared publications

Cognitive Systems, Eberhard Karls University, Tübingen, Germany

Hans Neubauer

60 shared publications

Department of Obstetrics and Gynecology, University Hospital and Medical Faculty of the Heinrich Heine University Düsseldorf, Düsseldorf, Germany

Nils Wiedemann

51 shared publications

Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany; BIOSS Centre for Biological Signalling Studies, University of Freiburg, 79104 Freiburg, Germany

Elmar Stickeler

49 shared publications

Department of Gynecology and Obstetrics, University Hospital Aachen

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Distribution of Articles published per year 
(2010 - 2018)
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13
 
Publications See all
Article 0 Reads 1 Citation Metabolic Phenotyping of Anks3 Depletion in mIMCD-3 cells - a Putative Nephronophthisis Candidate Manuel Schlimpert, Simon Lagies, Vadym Budnyk, Barbara Mulle... Published: 13 June 2018
Scientific Reports, doi: 10.1038/s41598-018-27389-y
DOI See at publisher website PubMed View at PubMed ABS Show/hide abstract
Nephronophthisis (NPH) is an autosomal recessive form of cystic kidney disease and the leading cause of hereditary kidney failure in children and young adults. Like other NPH proteins, the NPHP16/Anks6-interacting protein Anks3 has been identified to cause laterality defects in humans. However, the cellular functions of Anks3 remain enigmatic. We investigated the metabolic impact of Anks3 depletion in cultured murine inner medullary collecting duct cells via GC-MS profiling and LC-MS/MS analysis. Combined metabolomics successfully identified 155 metabolites; 48 metabolites were identified to be significantly altered by decreasing Anks3 levels. Especially, amino acid and purine/pyrimidine metabolism were affected by loss of Anks3. Branched-chain amino acids were identified to be significantly downregulated suggesting disrupted nutrient signalling. Tryptophan and 1-ribosyl-imidazolenicotinamide accumulated whereas NAD+ and NADP+ concentrations were diminished indicating disturbances within the tryptophan-niacin pathway. Most strikingly, nucleosides were reduced upon Anks3 depletion, while 5-methyluridine and 6-methyladenosine accumulated over time. Hence, elevated PARP1 and cleaved PARP1 levels could be detected. Furthermore, living cell number and viability was significantly declined. In combination, these results suggest that Anks3 may be involved in DNA damage responses by balancing the intracellular nucleoside pool.
Article 6 Reads 0 Citations Metabolic profiling of isolated mitochondria and cytoplasm reveals compartment-specific metabolic responses Daqiang Pan, Caroline Lindau, Simon Lagies, Nils Wiedemann, ... Published: 31 March 2018
Metabolomics, doi: 10.1007/s11306-018-1352-x
DOI See at publisher website PubMed View at PubMed ABS Show/hide abstract
Subcellular compartmentalization enables eukaryotic cells to carry out different reactions at the same time, resulting in different metabolite pools in the subcellular compartments. Thus, mutations affecting the mitochondrial energy metabolism could cause different metabolic alterations in mitochondria compared to the cytoplasm. Given that the metabolite pool in the cytosol is larger than that of other subcellular compartments, metabolic profiling of total cells could miss these compartment-specific metabolic alterations. To reveal compartment-specific metabolic differences, mitochondria and the cytoplasmic fraction of baker’s yeast Saccharomyces cerevisiae were isolated and subjected to metabolic profiling. Mitochondria were isolated through differential centrifugation and were analyzed together with the remaining cytoplasm by gas chromatography–mass spectrometry (GC–MS) based metabolic profiling. Seventy-two metabolites were identified, of which eight were found exclusively in mitochondria and sixteen exclusively in the cytoplasm. Based on the metabolic signature of mitochondria and of the cytoplasm, mutants of the succinate dehydrogenase (respiratory chain complex II) and of the FOF1-ATP-synthase (complex V) can be discriminated in both compartments by principal component analysis from wild-type and each other. These mitochondrial oxidative phosphorylation machinery mutants altered not only citric acid cycle related metabolites but also amino acids, fatty acids, purine and pyrimidine intermediates and others. By applying metabolomics to isolated mitochondria and the corresponding cytoplasm, compartment-specific metabolic signatures can be identified. This subcellular metabolomics analysis is a powerful tool to study the molecular mechanism of compartment-specific metabolic homeostasis in response to mutations affecting the mitochondrial metabolism. The online version of this article (10.1007/s11306-018-1352-x) contains supplementary material, which is available to authorized users.
Article 6 Reads 0 Citations Metabolic characterization of directly reprogrammed renal tubular epithelial cells (iRECs) Simon Lagies, Roman Pichler, Michael M. Kaminski, Manuel Sch... Published: 01 March 2018
Scientific Reports, doi: 10.1038/s41598-018-22073-7
DOI See at publisher website PubMed View at PubMed ABS Show/hide abstract
Fibroblasts can be directly reprogrammed to induced renal tubular epithelial cells (iRECs) using four transcription factors. These engineered cells may be used for disease modeling, cell replacement therapy or drug and toxicity testing. Direct reprogramming induces drastic changes in the transcriptional landscape, protein expression, morphological and functional properties of cells. However, how the metabolome is changed by reprogramming and to what degree it resembles the target cell type remains unknown. Using untargeted gas chromatography-mass spectrometry (GC-MS) and targeted liquid chromatography-MS, we characterized the metabolome of mouse embryonic fibroblasts (MEFs), iRECs, mIMCD-3 cells, and whole kidneys. Metabolic fingerprinting can distinguish each cell type reliably, revealing iRECs are most similar to mIMCD-3 cells and clearly separate from MEFs used for reprogramming. Treatment with the cytotoxic drug cisplatin induced typical changes in the metabolic profile of iRECs commonly occurring in acute renal injury. Interestingly, metabolites in the medium of iRECs, but not of mIMCD-3 cells or fibroblast could distinguish treated and non-treated cells by cluster analysis. In conclusion, direct reprogramming of fibroblasts into renal tubular epithelial cells strongly influences the metabolome of engineered cells, suggesting that metabolic profiling may aid in establishing iRECs as in vitro models for nephrotoxicity testing in the future.
PROCEEDINGS-ARTICLE 25 Reads 0 Citations Mitochondrial metabolomics reveals compartment-specific metabolic responses in yeast cells Bernd Kammerer, Daqiang Pan, Caroline Lindau, Simon Lagies, ... Published: 20 November 2017
Proceedings of The 2nd International Electronic Conference on Metabolomics, doi: 10.3390/iecm-2-04981
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Mutations in mitochondrial membrane proteins could cause physiological and metabolic alterations in mitochondria as well as in cytosol. In order to address the origin of these alterations, mitochondria and cytosol of yeast wild-type BY4741 and two mutants, sdh2Δ and atp4Δ, were isolated from whole cells. These three compartments, namely mitochondria, cytosol and whole cell, were analyzed by gas chromatography-mass spectrometry based metabolic profiling, identifying seventy-three metabolites altogether, from which sixteen or ten were not detected either in mitochondria or cytosol. Compartment-specific distribution and regulation of metabolites were observed, showing the responses to the deletions of sdh2 and atp4. Based on the metabolic signature in mitochondrial matrix and cytosol, both mutants can be discriminated from wild-type by principal component analysis. De letions of electron chain transport components, sdh2 and atp4, altered not only citrate cycle related metabolites, but also diverse metabolites including amino acids, fatty acids, purine and pyrimidine intermediates and others. By applying metabolomics to isolated mitochondria and cytosol, compartment-specific metabolic regulation can be identified, which is helpful in understanding the molecular mechanism of mitochondrial homeostasis in response to genetic mutations.
Article 0 Reads 2 Citations Metabolic Response to XD14 Treatment in Human Breast Cancer Cell Line MCF-7 Daqiang Pan, Michel Kather, Lucas Willmann, Manuel Schlimper... Published: 24 October 2016
International Journal of Molecular Sciences, doi: 10.3390/ijms17101772
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XD14 is a 4-acyl pyrrole derivative, which was discovered by a high-throughput virtual screening experiment. XD14 inhibits bromodomain and extra-terminal domain (BET) proteins (BRD2, BRD3, BRD4 and BRDT) and consequently suppresses cell proliferation. In this study, metabolic profiling reveals the molecular effects in the human breast cancer cell line MCF-7 (Michigan Cancer Foundation-7) treated by XD14. A three-day time series experiment with two concentrations of XD14 was performed. Gas chromatography-mass spectrometry (GC-MS) was applied for untargeted profiling of treated and non-treated MCF-7 cells. The gained data sets were evaluated by several statistical methods: analysis of variance (ANOVA), clustering analysis, principle component analysis (PCA), and partial least squares discriminant analysis (PLS-DA). Cell proliferation was strongly inhibited by treatment with 50 µM XD14. Samples could be discriminated by time and XD14 concentration using PLS-DA. From the 117 identified metabolites, 67 were significantly altered after XD14 treatment. These metabolites include amino acids, fatty acids, Krebs cycle and glycolysis intermediates, as well as compounds of purine and pyrimidine metabolism. This massive intervention in energy metabolism and the lack of available nucleotides could explain the decreased proliferation rate of the cancer cells.
Article 1 Read 0 Citations Hyperthermia-driven aberrations of secreted microRNAs in breast cancer in vitro Thalia Erbes, Marc Hirschfeld, Silvia Waldeck, Gerta Rücker,... Published: 05 July 2016
International Journal of Hyperthermia, doi: 10.3109/02656736.2016.1161832
DOI See at publisher website
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