摘要 :
The proteasome is a large protein complex responsible for proteolysis in cells. Though the proteasome is widely conserved in all eukaryotes, vertebrates additionally possess tissue-specific proteasomes, termed immunoproteasomes an...
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The proteasome is a large protein complex responsible for proteolysis in cells. Though the proteasome is widely conserved in all eukaryotes, vertebrates additionally possess tissue-specific proteasomes, termed immunoproteasomes and thymoproteasomes. These specialized proteasomes diverge from constitutive proteasomes in the makeup of their catalytic 20S core particle (CP), whereby the constitutive β1, β2, and β5 catalytic subunits are replaced by β1i, β2i, and β5i in immunoproteasomes, or β1i, β2i, and β5t in thymoproteasomes. However, as constitutive β1, β2, and β5 are also present in tissues and cells expressing immuno- and thymoproteasomes, the specialized proteasomes must be able to selectively incorporate their specific subunits. Here, we review the mechanisms governing the assembly of constitutive and specialized proteasomes elucidated thus far. Studies have revealed that β1i and β2i are added onto the α-ring of the CP prior to the other β subunits. Furthermore, β5i and β5t can be incorporated independent of β4, whereas constitutive β5 incorporation is dependent on β4. These mechanisms allow the immuno- and thymoproteasomes to integrate tissue-specific β-subunits without contamination from constitutive β1, β2, and β5. We end the review with a brief discussion on the diseases caused by mutations to the immunoproteasome and the proteins involved with its assembly.
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Acidic and neutral oligosaccharides (OSs) from goat milk or bovine colostrum were assessed for the potential uses as ingredients of infant formulae or functional foods. For that purpose, neutral and acidic OS fractions were isolat...
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Acidic and neutral oligosaccharides (OSs) from goat milk or bovine colostrum were assessed for the potential uses as ingredients of infant formulae or functional foods. For that purpose, neutral and acidic OS fractions were isolated by a modified charcoal column method. The elution protocol of the charcoal column was improved to decrease the column size to approximately 1/9 of the traditional process. Then the inhibitory potencies of the neutral and acidic OSs isolated from the two mammals were compared at 2.5 and 5.0 mg mL(-1) using OSs from human breast milk as a reference. These OS fractions inhibited the adhesion of Salmonella enterica to Caco-2 cells, although some differences were not statistically significant. Finally, goat milk OSs were determined as more potential ingredients of infant formulae or functional foods in the aspect of the potency of adherence inhibition, safety, and the availability of the starting material. (C) 2018 Elsevier Ltd. All rights reserved.
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Taking advantage of the enhanced permeation and retention (EPR) effect is a promising approach for delivering macromolecules or nanoparticles to tumors. Recent studies revealed that this strategy is also applicable for targeting o...
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Taking advantage of the enhanced permeation and retention (EPR) effect is a promising approach for delivering macromolecules or nanoparticles to tumors. Recent studies revealed that this strategy is also applicable for targeting other pathological lesions (i.e. inflammatory disease). In the present study, we report the optimal size of a nanoparticle for allowing the higher accumulation of a particle in an inflammatory lesion using a dextran sulfate sodium (DSS)-induced colitis model. As a nanoparticle platform, we utilized a SS-cleavable and pH-activated lipid-like material (ssPalm), that can be used to produce particles in a variety of sizes ranging from 50 nm to 180 nm while using the same lipid composition. In healthy mice, particle accumulation remained low regardless of size. In contrast, the accumulation in inflammatory colon tissue was enhanced depending on the progress of the inflammation. In this situation, the apparent uptake clearance accumulation of a mid-sized particle (113 nm on average) was higher than that for smaller and larger (54 nm and 183 nm in average, respectively) ones. Therefore, controlling particle size is an important parameter for the extensive targeting of inflammatory lesion. (C) 2016 Elsevier B.V. All rights reserved.
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