Activation of unfolded protein response pathway is important for valproic acid mediated increase in immunoglobulin G productivity in recombinant Chinese hamster ovary cells

The CHO (Chinese hamster ovary) glycosylation mutant cell line, B3F7, transfers the truncated glycan Glc3Man5GlcNAc2 on to nascent proteins. After deglucosylation, the resulting Man5GlcNAc2 glycan is subjected to two reciprocal enzymic processes: the action of an endoplasmic-reticulum (ER) kifunensine-sensitive α1,2-mannosidase activity to yield a Man4GlcNAc2 glycan, and the reglucosylation involved in the quality-control system which ensures that only correctly folded glycoproteins leave the ER. We show that the recombinant secreted alkaline phosphatase (SeAP) produced in stably transfected B3F7 cells, is co-immunoprecipitated with the GRP78 (glucose-regulated protein 78), a protein marker of the unfolded protein response (UPR). The level of GRP78 transcription has been evaluated by reverse transcription-PCR (RT-PCR) and we demonstrate that B3F7 cells present a constitutively higher level of UPR in the absence of inductors, compared with Pro−5 cells. Interestingly, a decrease was observed in the UPR and an increase in SeAP secretion in the kifunensine-treated B3F7 cells. Altogether, these data highlight the relationships between the glycan structure, the quality control system and the UPR. Moreover, they support the idea that a specific demannosylation step is a key event of the glycoprotein quality control in B3F7 cells.

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Malignancy-related characteristics of wild type and drug-resistant chinese hamster ovary cells

Pathology ◽

10.3109/00313029309066588 ◽

1993 ◽

Vol 25 (3) ◽

pp. 268-276 ◽

Cited By ~ 5

Author(s):

Wanda B. Mackinnon ◽

Marlen Dyne ◽

Rebecca Hancock ◽

Carolyn E. Mountford ◽

Adrienne J. Grant ◽

...

Keyword(s):

Chinese Hamster Ovary ◽

Chinese Hamster Ovary Cells ◽

Chinese Hamster ◽

Drug Resistant ◽

Wild Type ◽

Ovary Cells

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Faculty Opinions recommendation of Integrin alphaIIbbeta3 activation in Chinese hamster ovary cells and platelets increases clustering rather than affinity.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.2712967.2376067 ◽

2010 ◽

Author(s):

Myron Cybulsky ◽

Sharon Hyduk

Keyword(s):

Chinese Hamster Ovary ◽

Chinese Hamster Ovary Cells ◽

Chinese Hamster ◽

Ovary Cells

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Review of the current methods of Chinese Hamster Ovary (CHO) cells cultivation for production of therapeutic protein

Current Drug Discovery Technologies ◽

10.2174/1570163817666200312102137 ◽

2020 ◽

Vol 17 ◽

Cited By ~ 3

Author(s):

Shazid Md. Sharker ◽

Md. Atiqur Rahman

Keyword(s):

Chinese Hamster Ovary ◽

Cho Cells ◽

Mass Production ◽

Chinese Hamster Ovary Cells ◽

Chinese Hamster ◽

Therapeutic Protein ◽

Specific Productivity ◽

Ovary Cells ◽

Further Development ◽

Interesting Area

Most of clinical approved protein-based drugs or under in clinical trial have a profound impact in the treatment of critical diseases. The mammalian eukaryotic cells culture approaches, particularly the CHO (Chinese Hamster Ovary) cells are mainly used in the biopharmaceutical industry for the mass-production of therapeutic protein. Recent advances in CHO cell bioprocessing to yield recombinant proteins and monoclonal antibodies have enabled the expression of quality protein. The developments of cell lines are possible to upgrade specific productivity. As a result, it holds an interesting area for academic as well as industrial researchers around the world. This review will concentrate on the recent progress of the mammalian CHO cells culture technology and the future scope of further development for the mass-production of protein therapeutics.

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