caa a22 4500 445324821 CHVBK 20180317142716.0 cr unu---uuuuu 170323e20110401xx s 000 0 eng 10.1007/s10858-011-9490-8 doi (NATIONALLICENCE)springer-10.1007/s10858-011-9490-8 NMR-based metabolomics of mammalian cell and tissue cultures [Elektronische Daten] [Nelly Aranibar, Michael Borys, Nancy Mackin, Van Ly, Nicholas Abu-Absi, Susan Abu-Absi, Matthias Niemitz, Bernhard Schilling, Zheng Li, Barry Brock, Reb Russell II, Adrienne Tymiak, Michael Reily] NMR spectroscopy was used to evaluate growth media and the cellular metabolome in two systems of interest to biomedical research. The first of these was a Chinese hamster ovary cell line engineered to express a recombinant protein. Here, NMR spectroscopy and a quantum mechanical total line shape analysis were utilized to quantify 30 metabolites such as amino acids, Krebs cycle intermediates, activated sugars, cofactors, and others in both media and cell extracts. The impact of bioreactor scale and addition of anti-apoptotic agents to the media on the extracellular and intracellular metabolome indicated changes in metabolic pathways of energy utilization. These results shed light into culture parameters that can be manipulated to optimize growth and protein production. Second, metabolomic analysis was performed on the superfusion media in a common model used for drug metabolism and toxicology studies, in vitro liver slices. In this study, it is demonstrated that two of the 48 standard media components, choline and histidine are depleted at a faster rate than many other nutrients. Augmenting the starting media with extra choline and histidine improves the long-term liver slice viability as measured by higher tissues levels of lactate dehydrogenase (LDH), glutathione and ATP, as well as lower LDH levels in the media at time points out to 94h after initiation of incubation. In both models, media components and cellular metabolites are measured over time and correlated with currently accepted endpoint measures. Springer Science+Business Media B.V., 2011 Metabolomics nationallicence NMR nationallicence Liver slice nationallicence CHO cell nationallicence Bioreactor nationallicence Bioprocess nationallicence Aranibar Nelly Bristol-Myers Squibb Company, Route 206 and Province Line Road, 08540, Princeton, NJ, USA aut Borys Michael Bristol-Myers Squibb Company, 6000 Thompson Road, 13057, Syracuse, NY, USA aut Mackin Nancy Bristol-Myers Squibb Company, 6000 Thompson Road, 13057, Syracuse, NY, USA aut Ly Van Bristol-Myers Squibb Company, Route 206 and Province Line Road, 08540, Princeton, NJ, USA aut Abu-Absi Nicholas Bristol-Myers Squibb Company, 6000 Thompson Road, 13057, Syracuse, NY, USA aut Abu-Absi Susan Bristol-Myers Squibb Company, 6000 Thompson Road, 13057, Syracuse, NY, USA aut Niemitz Matthias PERCH Solutions Ltd., Hyrräkatu 3A1, 70500, Kuopio, Finland aut Schilling Bernhard Bristol-Myers Squibb Company, 6000 Thompson Road, 13057, Syracuse, NY, USA aut Li Zheng Bristol-Myers Squibb Company, 6000 Thompson Road, 13057, Syracuse, NY, USA aut Brock Barry Bristol-Myers Squibb Company, Route 206 and Province Line Road, 08540, Princeton, NJ, USA aut Russell II Reb Bristol-Myers Squibb Company, 311 Pennington-Rocky Hill Road, 08534, Pennington, NJ, USA aut Tymiak Adrienne Bristol-Myers Squibb Company, Route 206 and Province Line Road, 08540, Princeton, NJ, USA aut Reily Michael Bristol-Myers Squibb Company, Route 206 and Province Line Road, 08540, Princeton, NJ, USA aut Journal of Biomolecular NMR Springer Netherlands 49/3-4(2011-04-01), 195-206 0925-2738 49:3-4<195 2011 49 10858 https://doi.org/10.1007/s10858-011-9490-8 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10858-011-9490-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Aranibar Nelly Bristol-Myers Squibb Company, Route 206 and Province Line Road, 08540, Princeton, NJ, USA aut NATIONALLICENCE 700 1- Borys Michael Bristol-Myers Squibb Company, 6000 Thompson Road, 13057, Syracuse, NY, USA aut NATIONALLICENCE 700 1- Mackin Nancy Bristol-Myers Squibb Company, 6000 Thompson Road, 13057, Syracuse, NY, USA aut NATIONALLICENCE 700 1- Ly Van Bristol-Myers Squibb Company, Route 206 and Province Line Road, 08540, Princeton, NJ, USA aut NATIONALLICENCE 700 1- Abu-Absi Nicholas Bristol-Myers Squibb Company, 6000 Thompson Road, 13057, Syracuse, NY, USA aut NATIONALLICENCE 700 1- Abu-Absi Susan Bristol-Myers Squibb Company, 6000 Thompson Road, 13057, Syracuse, NY, USA aut NATIONALLICENCE 700 1- Niemitz Matthias PERCH Solutions Ltd., Hyrräkatu 3A1, 70500, Kuopio, Finland aut NATIONALLICENCE 700 1- Schilling Bernhard Bristol-Myers Squibb Company, 6000 Thompson Road, 13057, Syracuse, NY, USA aut NATIONALLICENCE 700 1- Li Zheng Bristol-Myers Squibb Company, 6000 Thompson Road, 13057, Syracuse, NY, USA aut NATIONALLICENCE 700 1- Brock Barry Bristol-Myers Squibb Company, Route 206 and Province Line Road, 08540, Princeton, NJ, USA aut NATIONALLICENCE 700 1- Russell II Reb Bristol-Myers Squibb Company, 311 Pennington-Rocky Hill Road, 08534, Pennington, NJ, USA aut NATIONALLICENCE 700 1- Tymiak Adrienne Bristol-Myers Squibb Company, Route 206 and Province Line Road, 08540, Princeton, NJ, USA aut NATIONALLICENCE 700 1- Reily Michael Bristol-Myers Squibb Company, Route 206 and Province Line Road, 08540, Princeton, NJ, USA aut NATIONALLICENCE 773 0- Journal of Biomolecular NMR Springer Netherlands 49/3-4(2011-04-01), 195-206 0925-2738 49:3-4<195 2011 49 10858 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer