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HEWL interacts with dissipated oleic acid micelles, and decreases oleic acid cytotoxicity.

ABSTRACT: Senile plaques are well-known hallmarks of Alzheimer's Diseases (AD). However, drugs targeting tangles of the protein tau and plaques of ?-amyloid have no significant effect on disease progression, and the studies on the underlying mechanism of AD remain in high demand. Growing evidence supports the protective role of senile plaques in local inflammation driven by S100A9. We herein demonstrate that oleic acid (OA) micelles interact with hen egg white lysozyme (HEWL) and promote its amyloid formation. Consequently, SH-SY5Y cell line and mouse neural stem cells are rescued from OA toxicity by co-aggregation of OA and HEWL. Using atomic force microscopy in combination with fluorescence microscopy, we revealed that HEWL forms round-shaped aggregates in the presence of OA micelles instead of protofibrils of HEWL alone. These HEWL amyloids act as a sink for toxic OA micelles and their co-aggregate form large clumps, suggesting a protective function in amyloid and OA cytotoxicity.

SUBMITTER: Huang Q

PROVIDER: S-EPMC6386356 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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HEWL interacts with dissipated oleic acid micelles, and decreases oleic acid cytotoxicity.

Huang Qin Q Sun Dan D Zubair Hussain Muhammad M Liu Yonggang Y A Morozova-Roche Ludmilla L Zhang Ce C

PloS one 20190222 2

Senile plaques are well-known hallmarks of Alzheimer's Diseases (AD). However, drugs targeting tangles of the protein tau and plaques of β-amyloid have no significant effect on disease progression, and the studies on the underlying mechanism of AD remain in high demand. Growing evidence supports the protective role of senile plaques in local inflammation driven by S100A9. We herein demonstrate that oleic acid (OA) micelles interact with hen egg white lysozyme (HEWL) and promote its amyloid forma ...[more]

PMID: 30794655

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Project description:Polymeric micelles combining the advantages of biocompatible poly- and oligosaccharides with classical micellar amphiphilic systems represent a promising class of drug carriers. In this work, micelles based on chitosan (or cyclodextrin) and oleic acid with various modification degrees were synthesized-the most optimal grafting degree is 15-30% in terms of CMC. According to NTA data, micelles have a hydrodynamic diameter of the main fraction of 60-100 nm. The inclusion of the antibacterial agents: moxifloxacin or rifampicin in micelles was studied by FTIR spectroscopy and fluorescence spectroscopy using a pyrene label (using monomer-excimer approach). When aromatic molecules are incorporated into micelles, the absorption bands of C-H bonds of the fatty tails of micelles shift towards smaller wavenumbers, indicating a stabilization of the micelles structure, and the microenvironment of the drug molecule changes according to the low frequencies shift and intensity changes in oscillation frequencies of 1450 cm-1 corresponding to aromatic fragment. Loading of moxifloxacin and rifampicin into micelles leads to a change in the fluorescent properties: a shift of the maximum of fluorescence emission to the long-wavelength region and an increase in the fluorescence anisotropy due to a drastic increase in the hydrodynamic volume of the fluorophore-containing rotating fragment. Using the pyrene label, the critical micelle concentrations were determined: from 4 to 30 nM depending on the polymer composition. Micellar systems enhance the effect of the antibiotic by increasing the penetration into bacterial cells and storing the drug in a protective coat. As a part of the supramolecular structure, the antibiotic remains active for more than four days, while in free form, the activity decreases after two days. In pharmacokinetic experiments, in vivo moxifloxacin in micellar systems show 1.7 times more efficiency compared to free form; moreover, two times higher maximal concentration in the blood is achieved. The advantage of polymer micellar systems in comparison with simple cyclodextrins and chitosan, which do not so significantly contribute to the antibacterial and pharmacokinetic parameters, was shown. Thus, polymeric micelles are one of the key approaches to improving the effectiveness of antibacterial drugs and solving the problems of resistant bacterial infections and multidrug resistance.

Dataset Information

HEWL interacts with dissipated oleic acid micelles, and decreases oleic acid cytotoxicity.

Publications

HEWL interacts with dissipated oleic acid micelles, and decreases oleic acid cytotoxicity.

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