Metabolic characterization of a hyper-productive state in an antibody producing NS0 myeloma cell line |
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| Authors: | Soo Hean Gary Khoo Mohamed Al-Rubeai |
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| Affiliation: | 1. Department of Chemical Engineering, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK;2. School of Chemical and Bioprocess Engineering, and Conway Institute for Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland;1. Unidad de Neumología Pediátrica y Fibrosis Quística, Hospital Universitari Vall d’Hebron, Barcelona, Spain;2. Departament de Pediatria, d’Obstetricia i Ginecologia i de Medicina Preventiva, Universitat Autònoma de Barcelona, Barcelona, Spain;3. Servicio de Cirugía Torácica, Hospital Universitari Vall d’Hebron, Barcelona, Spain;4. Servicio de Neumología, Hospital Universitari Vall d’Hebron, Barcelona, Spain;5. CIBER Enfermedades Respiratorias (CIBERES), Spain;1. Department of Chemistry, University of Kalyani, Kalyani, Nadia 741235, WB, India;2. Department of Physics, Acharya Prafulla Chandra College, New Barrackpore, Kolkata 700131, India;3. Immunology Laboratory, Department of Zoology, University of Calcutta, 35 Ballygunge Circular Road, Kolkata 700019, India;4. Department of Chemistry, Missouri University of S & T, Rolla, MO 65409, USA;1. UCCS UMR-CNRS 8181, Université de Lille1, Villeneuve d''Ascq, France;2. LASIR UMR-CNRS 8516, Université de Lille1, Villeneuve d''Ascq, France;3. IMMCL CNRS-FR2638, Université de Lille1, Villeneuve d''Ascq, France;1. Division of Hematology and Oncology, Icahn School of Medicine at Mount Sinai, New York, NY;2. Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY;1. Department of Physics, Faculty of Science, Damietta University, Damietta 34517, Egypt;2. Department of Chemistry, Faculty of Science, Damietta University, Damietta 34517, Egypt;1. Department of Chemistry, St. Joseph’s College, Tiruchirapalli 620 002, Tamil Nadu, India;2. Department of Physics, A.V.C. College, Mayiladuthurai 609 305, Tamil Nadu, India;3. Department of Chemistry, National Institute of Technology, Tiruchirapalli 620 015, Tamil Nadu, India;4. Nanotechnology Centre, University of Bahrain, Bahrain |
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| Abstract: | Metabolic profiling or metabolomics is the analysis of a larger number of small metabolic compounds within cells. While this technique has been utilized to study microbial and yeast strains under different physiochemical conditions, very little has been reported regarding its application in mammalian cell culture. Here, the physiological and metabolic changes observed during the proliferation arrest of an antibody producing GS-NS0 mouse myeloma cell line were studied using conventional biochemical analysis and one-dimensional nuclear magnetic resonance (NMR)-based metabolic profiling. Proliferation-arrested cells had increased antibody productivity, enhanced normalized mitochondrial membrane potential, and showed changes in the consumption of several amino acids. Further investigation into these physiological changes was carried out by 1H NMR profiling followed by principle component analysis (PCA). The resulting data showed a clear separation of the arrested and control spectra that related to the altered metabolic state of the arrested culture. Metabolites associated with phosphatidylcholine homeostasis, lipid and fatty acid metabolism, and ascorbate formation were found to be present in significant amount in these cultures. Taken together, the results suggested that there was a link between the metabolic alterations and the hyper-productive state, possibly relating to vesicle recycling and secretory functions, and mechanism to counteract against the generation of reactive oxygen species. While the use of metabolic profiling is still in its infancy, its potential to enhance the understanding of physiological processes in mammalian cell lines used for antibody production is certain. |
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