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Exopolysaccharide Production from Marine Bacteria and Its Applications
Published in Se-Kwon Kim, Marine Biochemistry, 2023
Prashakha J. Shukla, Shivang B. Vhora, Ankita G. Murnal, Unnati B. Yagnik, Maheshwari Patadiya
Most of the carbohydrate polymers are assembled by the Wzx/Wzy-dependent pathway due to their highly diverse sugar pattern (4–5 sugars) and therefore are called heteropolymers. This pathway uses two types of enzymes: flippase (Wzx) and polymerase (Wzy; Figure 18.1; Schmid et al., 2015; Parkar et al., 2016).
Characteristics, Events, and Stages in Tumorigenesis
Published in Franklyn De Silva, Jane Alcorn, The Elusive Road Towards Effective Cancer Prevention and Treatment, 2023
Franklyn De Silva, Jane Alcorn
Microvesicles are produced from the plasma membrane through direct outward budding (and fission) with subsequent release into the extracellular space [830, 857, 896]. Membrane lipid curvature plays an important role for either inward-budding vesicle formation within the endocytic system (exosomes) or an outward-budding vesicle formation at the plasma membrane (microvesicles) [831]. Some of the biogenetic mechanisms involved include flippase, flippase and scramblase (TMEM16F), amino-phospholipid translocases, ARF6, membrane curvature, cytoskeleton, and asymmetric movement of phosphatidylserine [769, 840, 897–900]. From plasma membranes of prostate and breast cancer cells, the shedding of cancer-derived MVs is attributed to the ADP-ribosylation factor 6 (ARF6) that is enriched in MVs [851, 901]. EVs, (especially exosomes), have been identified as major modes by which cells interact with each other, including stromal cells, within the tumor microenvironment [849].
Plant-Based Compounds as Alternative Adjuvant Therapy for Multidrug-Resistant Cancer
Published in Parimelazhagan Thangaraj, Phytomedicine, 2020
E. C. Aniogo, Blassan P. George, Heidi Abrahamse
One of the most widely known resistance mechanisms is through altered membrane transport by adenosine triphosphate (ATP)-binding cassette (ABC) transporters. The ABC transporters belong to the ubiquitous superfamily of transmembrane proteins that modulate drug and other biomolecules absorption, distribution, and excretion across cell membrane. Today, there are 48 identified human ABC genes grouped into seven subclasses (A–G) based on their sequence of homology and genomic organization (Chorawala et al. 2012; Eid et al. 2015). In clinical transport-associated multidrug resistance, the MDR1 gene, which encodes for P-glycoprotein (P-gp; MDR1, ABCB1), is the widely studied. The P-gp has two highly hydrophobic integral membrane and nucleotide-binding domains that make up its structure. This structure enables them to efficiently efflux cytotoxic drugs through a “pump” and “flippase” model of transport from the inner leaflet to the outer leaflet of the lipid bilayer into the extracellular space (Sharom 2014). Other ABC transporters: the multidrug resistance-associated protein 1 (MRP-1, ABCC1) and the breast cancer-resistant protein (BCRP, ABCG2) have been implicated as major efflux transporters responsible for cancer resistance in chemotherapy (Mao and Unadkat 2015). The MRP1 is similar in structure with the P-gp/MDR1 and contains an added amino terminal in the domains attached to the core that can recognize both neutral and anionic hydrophobic natural products and transports glutathione (Eid et al. 2015). The ABCG2 gene located at 4q22 encodes human BCRP. Structurally, the BCRP contains an ATP-binding domain and six transmembrane segments in a homodimer of two-half transporters. The BCRP is highly expressed and widely distributed in the gastrointestinal tract, excretory tissue, and blood-tissue barriers (Fletcher et al. 2016).
Assessing regulated cell death modalities as an efficient tool for in vitro nanotoxicity screening: a review
Published in Nanotoxicology, 2023
Anton Tkachenko, Anatolii Onishchenko, Valeriy Myasoedov, Svetlana Yefimova, Ondrej Havranek
Nanomaterials-triggered intracellular Ca2+ elevation promotes Gardos channel-mediated K+ efflux driving cell shrinkage, which is a hallmark of eryptosis. Moreover, elevated Ca2+ is known to inhibit flippase and activate scramblase. These enzymes maintain the phospholipid asymmetry in cell membranes and their Ca2+-mediated dysregulation causes the cell membrane phospholipid scrambling with phosphatidylserine externalization detectable by annexin V staining (Föller and Lang 2020). This is a typical characteristic of eryptosis used in all studies that analyzed the ability of nanomaterials to induce eryptosis. The exposed phosphatidylserine is detected by macrophages as an ‘eat-me’ signal and eryptotic red blood cells are consequently eliminated from the bloodstream through efferocytosis (Chang et al. 2018). On top of that, eryptotic erythrocytes with exposed phosphatidylserine may promote blood coagulation, which can also substantially contribute to the nanoparticles-induced toxicity (de la Harpe et al. 2019). The additional effect of Ca2+ influx is calpain activation, which in turn leads to erythrocyte cytoskeleton degradation (Lang et al. 2006) (Figure 2).
Gene of the issue: ANO6 and Scott Syndrome
Published in Platelets, 2020
Sarah L. Millington-Burgess, Matthew T. Harper
PS is normally restricted to the inner leaflet of the plasma membrane by inward ‘flippase’ activity (Figure 1). Procoagulant platelet stimuli, such as dual stimulation with collagen and thrombin, or a Ca2+ ionophore, trigger a large, sustained increase in cytosolic Ca2+. This inhibits flippase activity and activates a ‘scramblase’ activity – bidirectional, nonselective movement of phospholipids, leading to loss of membrane asymmetry. Flippase activity is unaffected in Scott Syndrome patients but the scramblase activity is defective [15,16]. As a result, PS exposure is almost completely abolished in Scott Syndrome platelets following stimulation [1]. Platelet microparticle release, which requires PS exposure, is also abolished [17]. Procoagulant platelets resemble necrotic cells, with a diluted cytoplasm, few remaining organelles and rapid swelling into large ‘balloon’-like structures [18,19]. Procoagulant ballooning is also diminished in Scott Syndrome platelets [20,21].
Improving protein glycan coupling technology (PGCT) for glycoconjugate vaccine production
Published in Expert Review of Vaccines, 2020
Jennifer Mhairi Dow, Marta Mauri, Timothy Alexander Scott, Brendan William Wren
In PGCT, the glycan is heterologously expressed in E. coli from a recombinant O-antigen or capsule biosynthetic gene cluster [34]. The glycan is progressively assembled onto the glycolipid carrier undecaprenyl pyrophosphate (Und-PP) on the cytoplasmic side of the inner membrane to form a lipid-linked oligosaccharide (LLO) [35,36]. A flippase, found in the heterologously expressed gene cluster then flips the LLO to the periplasmic face where a polymerase can build upon it [37]. Once fully assembled, an OST such as PglB couples the glycan by the reducing end sugar (first sugar of the oligosaccharide chain) to any periplasmic protein containing the consensus acceptor sequon (Figure 1(a)) [33,38]. These founding discoveries have been built upon to enhance the capacity of PGCT, and we discuss each of the components in detail in Section 2.