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• W4220723339 endingPage "2586" @default.
• W4220723339 startingPage "2569" @default.
• W4220723339 abstract "Abstract Chinese hamster ovary (CHO) cells are the most commonly used host cell lines for therapeutic protein production. Exposure of these cells to highly concentrated feed solution during fed-batch cultivation can lead to a non-physiological increase in osmolality (> 300 mOsm/kg) that affects cell physiology, morphology, and proteome. As addressed in previous studies (and indeed, as recently addressed in our research), hyperosmolalities of up to 545 mOsm/kg force cells to abort proliferation and gradually increase their volume—almost tripling it. At the same time, CHO cells also show a significant hyperosmolality-dependent increase in mitochondrial activity. To gain deeper insight into the molecular mechanisms that are involved in these processes, as detailed in this paper, we performed a comparative quantitative label-free proteome study of hyperosmolality-exposed CHO cells compared with control cells. Our analysis revealed differentially expressed key proteins that mediate mitochondrial activation, oxidative stress amelioration, and cell cycle progression. Our studies also demonstrate a previously unknown effect: the strong regulation of proteins can alter both cell membrane stiffness and permeability. For example, we observed that three types of septins (filamentous proteins that form diffusion barriers in the cell) became strongly up-regulated in response to hyperosmolality in the experimental setup. Overall, these new observations correlate well with recent CHO-based fluxome and transcriptome studies, and reveal additional unknown proteins involved in the response to hyperosmotic pressure by over-concentrated feed in mammalian cells. Key points • First-time comparative proteome analysis of CHO cells exposed to over-concentrated feed. • Discovery of membrane barrier-forming proteins up-regulation under hyperosmolalit y. • Description of mitochondrial and protein chaperones activation in treated cells ." @default.
• W4220723339 created "2022-04-03" @default.
• W4220723339 creator A5018449566 @default.
• W4220723339 creator A5023425193 @default.
• W4220723339 creator A5046548445 @default.
• W4220723339 creator A5062194813 @default.
• W4220723339 date "2022-03-21" @default.
• W4220723339 modified "2023-09-25" @default.
• W4220723339 title "Hyperosmolality in CHO cell culture: effects on the proteome" @default.
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• W4220723339 doi "https://doi.org/10.1007/s00253-022-11861-x" @default.
• W4220723339 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35312825" @default.
• W4220723339 hasPublicationYear "2022" @default.
• W4220723339 type Work @default.
• W4220723339 citedByCount "2" @default.

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