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In recent years, there has been a remarkable surge in the approval of therapeutic protein drugs, particularly recombinant glycoproteins. Drosophila melanogaster S2 cells have become an appealing platform for the production of recombinant proteins due to their simplicity and low cost in cell culture. However, a significant limitation associated with using the S2 cell expression system is its propensity to introduce simple paucimannosidic glycosylation structures, which differs from that in the mammalian expression system. It is well established that the glycosylation patterns of glycoproteins have a profound impact on the physicochemical properties, bioactivity, and immunogenicity. Therefore, understanding the mechanisms behind these glycosylation modifications and implementing measures to address it has become a subject of considerable interest. This review aims to comprehensively summarize recent advancements in glycosylation modification in S2 cells, with a particular focus on comparing the glycosylation patterns among S2, other insect cells, and mammalian cells, as well as developing strategies for altering the glycosylation patterns of recombinant glycoproteins.
In recent years, there has been a remarkable surge in the approval of therapeutic protein drugs, particularly recombinant glycoproteins. Drosophila melanogaster S2 cells have become an appealing platform for the production of recombinant proteins due to their simplicity and low cost in cell culture. However, a significant limitation associated with using the S2 cell expression system is its propensity to introduce simple paucimannosidic glycosylation structures, which differs from that in the mammalian expression system. It is well established that the glycosylation patterns of glycoproteins have a profound impact on the physicochemical properties, bioactivity, and immunogenicity. Therefore, understanding the mechanisms behind these glycosylation modifications and implementing measures to address it has become a subject of considerable interest. This review aims to comprehensively summarize recent advancements in glycosylation modification in S2 cells, with a particular focus on comparing the glycosylation patterns among S2, other insect cells, and mammalian cells, as well as developing strategies for altering the glycosylation patterns of recombinant glycoproteins.
Reduced responsiveness of precursor B-acute lymphoblastic leukemia (BCP-ALL) to chemotherapy can be first detected in the form of minimal residual disease leukemia cells that persist after 28 days of initial treatment. The ability of these cells to resist chemotherapy is partly due to the microenvironment of the bone marrow, which promotes leukemia cell growth and provides protection, particularly under these conditions of stress. It is unknown if and how the glycocalyx of such cells is remodelled during the development of tolerance to drug treatment, even though glycosylation is the most abundant cell surface post-translational modification present on the plasma membrane. To investigate this, we performed omics analysis of BCP-ALL cells that survived a 30-day vincristine chemotherapy treatment while in co-culture with bone marrow stromal cells. Proteomics showed decreased levels of some metabolic enzymes. Overall glycocalyx changes included a shift from Core-2 to less complex Core-1 O-glycans, and reduced overall sialylation, with a shift from alpha2-6 to alpha2-3 linked Neu5Ac. Interestingly, there was a clear increase in bisecting complex N-glycans with a concomitant increased mRNA expression of MGAT3, the only enzyme known to form bisecting N-glycans. These small but reproducible quantitative differences suggest that individual glycoproteins become differentially glycosylated. Glycoproteomics confirmed glycosite specific modulation of cell surface and lysosomal proteins in drug-tolerant BCP-ALL cells, including HLA-DRA, CD38, LAMP1 and PPT1. We conclude that drug-tolerant persister leukemia cells that grow under continuous chemotherapy stress have characteristic glycotraits that correlate with and perhaps contribute to their ability to survive and could be tested as neoantigens in drug-resistant leukemia.
N-acetylglucosamine (GlcNAc) is an endogenous compound whose intracellular concentration is closely associated with the biosynthesis of acetyllactosamine-rich N-linked oligosaccharides. These oligosaccharides interact with mammalian lectin galectin-3, mediating cell surface receptor dynamics as well as cell-to-cell and cell-to-extracellular matrix interactions. Our previous and recent studies suggest that GlcNAc, in conjunction with galectin-3, augments muscle regenerationin vitro. We have also demonstrated that intraperitoneal GlcNAc administration improves muscle strength in a murine model of Duchenne muscular dystrophy (DMD) (mdxmice). Here, we show that oral administration of GlcNAc significantly improves the spontaneous locomotor activity of mdx mice. Administering GlcNAc at concentrations of 0.6, 1.2, 1.8, and 2.4 g/kg body weight per day for 35 days significantly improved nocturnal spontaneous locomotor activity at all those doses, with the 1.2 g/kg body weight dose reducing damages of extensor digitorum longus muscle by nearly 50%. While consecutive forced exercises, including horizontal and downhill treadmill running, reduced GlcNAc-promoted locomotor activity, treatment with 0.6 and 1.2 g/kg body weight treatment results in increased spontaneous locomotor activity. These results suggest that GlcNAc enhances overall muscle health, likely through promoting muscle repair/regeneration rather than preventing damage formation. Notably, co-administration of GlcNAc with prednisolone, a corticosteroid commonly used in DMD patients, further enhanced spontaneous locomotor improvement inmdxmice compared to prednisolone alone. These findings suggest that GlcNAc has the potential to improve the clinical status of DMD patients, either as a monotherapy or in combination with corticosteroids.
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