TY  - JOUR
A1  - Schmitz, Werner
A1  - Koderer, Corinna
A1  - El-Mesery, Mohamed
A1  - Gobik, Sebastian
A1  - Sampers, Rene
A1  - Straub, Anton
A1  - Kübler, Alexander Christian
A1  - Seher, Axel
T1  - Metabolic fingerprinting of murine L929 fibroblasts as a cell-based tumour suppressor model system for methionine restriction
JF  - International Journal of Molecular Sciences
N2  - Since Otto Warburg reported in 1924 that cancer cells address their increased energy requirement through a massive intake of glucose, the cellular energy level has offered a therapeutic anticancer strategy. Methionine restriction (MetR) is one of the most effective approaches for inducing low-energy metabolism (LEM) due to the central position in metabolism of this amino acid. However, no simple in vitro system for the rapid analysis of MetR is currently available, and this study establishes the murine cell line L929 as such a model system. L929 cells react rapidly and efficiently to MetR, and the analysis of more than 150 different metabolites belonging to different classes (amino acids, urea and tricarboxylic acid cycle (TCA) cycles, carbohydrates, etc.) by liquid chromatography/mass spectrometry (LC/MS) defines a metabolic fingerprint and enables the identification of specific metabolites representing normal or MetR conditions. The system facilitates the rapid and efficient testing of potential cancer therapeutic metabolic targets. To date, MS studies of MetR have been performed using organisms and yeast, and the current LC/MS analysis of the intra- and extracellular metabolites in the murine cell line L929 over a period of 5 days thus provides new insights into the effects of MetR at the cellular metabolic level.
KW  - methionine restriction
KW  - caloric restriction
KW  - mass spectrometry
KW  - LC/MS
KW  - liquid chromatography/mass spectrometry
KW  - metabolism
KW  - L929
KW  - amino acid
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-259198
SN  - 1422-0067
VL  - 22
IS  - 6
ER  - 
TY  - JOUR
A1  - Koderer, Corinna
A1  - Schmitz, Werner
A1  - Wünsch, Anna Chiara
A1  - Balint, Julia
A1  - El-Mesery, Mohamed
A1  - Volland, Julian Manuel
A1  - Hartmann, Stefan
A1  - Linz, Christian
A1  - Kübler, Alexander Christian
A1  - Seher, Axel
T1  - Low energy status under methionine restriction is essentially independent of proliferation or cell contact inhibition
JF  - Cells
N2  - Nonlimited proliferation is one of the most striking features of neoplastic cells. The basis of cell division is the sufficient presence of mass (amino acids) and energy (ATP and NADH). A sophisticated intracellular network permanently measures the mass and energy levels. Thus, in vivo restrictions in the form of amino acid, protein, or caloric restrictions strongly affect absolute lifespan and age-associated diseases such as cancer. The induction of permanent low energy metabolism (LEM) is essential in this process. The murine cell line L929 responds to methionine restriction (MetR) for a short time period with LEM at the metabolic level defined by a characteristic fingerprint consisting of the molecules acetoacetate, creatine, spermidine, GSSG, UDP-glucose, pantothenate, and ATP. Here, we used mass spectrometry (LC/MS) to investigate the influence of proliferation and contact inhibition on the energy status of cells. Interestingly, the energy status was essentially independent of proliferation or contact inhibition. LC/MS analyses showed that in full medium, the cells maintain active and energetic metabolism for optional proliferation. In contrast, MetR induced LEM independently of proliferation or contact inhibition. These results are important for cell behaviour under MetR and for the optional application of restrictions in cancer therapy.
KW  - methionine restriction
KW  - caloric restriction
KW  - mass spectrometry
KW  - LC/MS
KW  - liquid chromatography/mass spectrometry
KW  - metabolomics
KW  - L929
KW  - amino acid
KW  - proliferation
KW  - contact inhibition
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-262329
SN  - 2073-4409
VL  - 11
IS  - 3
ER  -