ABSTRACT
Oligomannuronic acid (MOS) from seaweed has antioxidant and anti-inflammatory activities. In this study, MOS was activated at the terminal to obtain three different graft complexes modified with sialic acid moiety (MOS-Sia). The results show that MOS-Sia addition can reduce the ß-structure formation of Aß42, and the binding effect of MOS-Sia3 is more obvious. MOS-Sia conjugates also have a better complexing effect with Ca2+ while reducing the formation of Aß42 oligomers in solutions. MOS-Sia3 (25-50 µg/mL) can effectively inhibit the activation state of BV-2 cells stimulated by Aß42, whereas a higher dose of MOS-Sia3 (>50 µg/mL) can inhibit the proliferation of BV-2 cells to a certain extent. A lower dose of MOS-Sia3 can also inhibit the expression of IL-1ß, IL-6, TNF-α, and other proinflammatory factors in BV-2 cells induced by Aß42 activation. In the future, the MOS-Sia3 conjugate can be used to treat Alzheimer's disease.
Subject(s)
Alginic Acid/metabolism , Amyloid beta-Peptides/metabolism , Amyloid beta-Peptides/pharmacology , Anti-Inflammatory Agents/pharmacology , Microglia/drug effects , Microglia/metabolism , N-Acetylneuraminic Acid/metabolism , Peptide Fragments/metabolism , Peptide Fragments/pharmacology , Protein Aggregates/drug effects , Protein Aggregation, Pathological/metabolism , Alzheimer Disease/metabolism , Animals , Cell Line, Transformed , Cell Proliferation/drug effects , Cell Survival/drug effects , Cytokines/metabolism , Mice , Signal Transduction/drug effectsABSTRACT
Polysialic acid (PSA), an acidic polysaccharide usually exists as a double-chain structure on cell adhesion molecules in vertebrates. The available PSA produced from Escherichia coli fermentation, however, is monochain PSA. In this work, a biomimetic biantenna type PSA (biPSA) was synthesized in vitro under mild conditions, and the terminal nonreducing ends of sialic acid residue were retained. The structure of biPSA was characterized through infrared spectroscopy, and NMR, and the double-chain structure of biPSA was confirmed by the doubled molecular weight and particle size of biPSA. Analysis through circular dichroism, isothermal titration calorimetry, and thermostability experiments revealed that the obtained biPSA was more stable in aqueous solution than PSA, especially after complexation with Ca2+, which increased the variation in enthalpy and entropy. However, the addition of Cu2+ had a negligible effect on configuration of PSA and biPSA. The addition of Ca2+ promoted cell proliferation in a culture of microglia BV-2 cells with biPSA in medium. By contrast, the addition of Cu2+ had toxic effects. Supplementation with biPSA can maintain cell viability for a longer period than supplementation with monochain PSA. This work indicates that biPSA is a potential substitute for monochain PSA in practical applications.