title: Metabolic analysis of antibody producing Chinese hamster ovary cell culture under different stresses conditions.
abstract: Chinese hamster ovary (CHO) cells are commonly used as the host cell lines concerning their ability to produce therapeutic proteins with complex post-translational modifications. In this study, we have investigated the time course extra- and intracellular metabolome data of the CHO-K1 cell line, under a control and stress conditions. The addition of NaCl and trehalose greatly suppressed cell growth, where the maximum viable cell density of NaCl and trehalose cultures were 2.2-fold and 2.8-fold less than that of a control culture. Contrariwise, the antibody production of both the NaCl and trehalose cultures was sustained for a longer time to surpass that of the control culture. The NaCl and trehalose cultures showed relatively similar dynamics of cell growth, antibody production, and substrate/product concentrations, while they indicated different dynamics from the control culture. The principal component analysis of extra- and intracellular metabolome dynamics indicated that their dynamic behaviors were consistent with biological functions. The qualitative pattern matching classification and hierarchical clustering analyses for the intracellular metabolome identified the metabolite clusters whose dynamic behaviors depend on NaCl and trehalose. The volcano plot revealed several reporter metabolites whose dynamics greatly change between in the NaCl and trehalose cultures. The elastic net identified some critical, intracellular metabolites that are distinct between the NaCl and trehalose. While a relatively small number of intracellular metabolites related to the cell growth, glucose, glutamine, lactate and ammonium ion concentrations, the mechanism of antibody production was suggested to be very complicated or not to be explained by elastic net regression analysis.
authors.affiliation: Department of Bioscience and Bioinformatics, Kyushu Institute of Technology, 680-4 Kawazu, Iizuka, Fukuoka 820-8502, Japan. Electronic address: badsha.md685@mail.kyutech.jp.
authors.forename: Md Bahadur
authors.initials: MB
authors.lastname: Badsha
authors.affiliation: Department of Bioscience and Bioinformatics, Kyushu Institute of Technology, 680-4 Kawazu, Iizuka, Fukuoka 820-8502, Japan; Biomedical Informatics R&D Center, Kyushu Institute of Technology, 680-4 Kawazu, Iizuka, Fukuoka 820-8502, Japan. Electronic address: kurata@bio.kyutech.ac.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kurata
authors.affiliation: Institute of Technology and Science, Tokushima University, 2-1 Minamijosanjima-cho, Tokushima 770-8506, Japan. Electronic address: onitsuka@tokushima-u.ac.jp.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Onitsuka
authors.affiliation: Human Metabolome Technologies, Inc., 24 Denby Road, Suite 217, Boston, MA 02134, USA. Electronic address: takushi.oga@humanmetabolome.com.
authors.forename: Takushi
authors.initials: T
authors.lastname: Oga
authors.affiliation: Department of Biotechnology, Graduate School of Engineering, Osaka University, U1E801, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address: omasa@bio.eng.osaka-u.ac.jp.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Omasa
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D016466:CHO Cells; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016000:Cluster Analysis; D006224:Cricetinae; D003412:Cricetulus; D005947:Glucose / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D055442:Metabolome / Q000187:drug effects*; D055432:Metabolomics; D025341:Principal Component Analysis; D011499:Protein Processing, Post-Translational; D012965:Sodium Chloride / Q000494:pharmacology*; D013997:Time Factors; D014199:Trehalose / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D005973:Glutamine; D019344:Lactic Acid; D012965:Sodium Chloride; D014199:Trehalose; D005947:Glucose
keywords: Antibody production; Biotechnology; Cell growth; Chinese hamster ovary cells; Metabolomics; NaCl and trehalose culture; Statistical analysis