Anti-amyloidogenic effect of artemin on α-synuclein

2020 ◽  
Vol 401 (10) ◽  
pp. 1143-1151
Author(s):  
Narges Marvastizadeh ◽  
Bahareh Dabirmanesh ◽  
Reza H. Sajedi ◽  
Khosro Khajeh

Abstractα-Synuclein fibrillation is now regarded as a major pathogenic process in Parkinson’s disease and its proteinaceous deposits are also detected in other neurological disorders including Alzheimer's disease. Therefore anti-amyloidegenic compounds may delay or prevent the progression of synucleinopathies disease. Molecular chaperones are group of proteins which mediate correct folding of proteins by preventing unsuitable interactions which may lead to aggregation. The objective of this study was to investigate the anti-amyloidogenic effect of molecular chaperone artemin on α-synuclein. As the concentration of artemin was increased up to 4 μg/ml, a decrease in fibril formation of α-synuclein was observed using thioflavin T (ThT) fluorescence and congo red (CR) assay. Transmission electron microscopy (TEM) images also demonstrated a reduction in fibrils in the presence of artemin. The secondary structure of α-synuclein was similar to its native form prior to fibrillation when incubated with artemin. A cell-based assay has shown that artemin inhibits α-synuclein aggregation and reduce cytotoxicity, apoptosis and reactive oxygen species (ROS) production. Our results revealed that artemin has efficient chaperon activity for preventing α-synuclein fibril formation and toxicity.

2019 ◽  
Vol 0 (0) ◽  
Author(s):  
Narges Marvastizadeh ◽  
Bahareh Dabirmanesh ◽  
Reza H. Sajedi ◽  
Khosro Khajeh

Abstract α-Synuclein fibrillation is now regarded as a major pathogenic process in Parkinson’s disease and its proteinaceous deposits are also detected in other neurological disorders including Alzheimer's disease. Therefore anti-amyloidegenic compounds may delay or prevent the progression of synucleinopathies disease. Molecular chaperones are group of proteins which mediate correct folding of proteins by preventing unsuitable interactions which may lead to aggregation. The objective of this study was to investigate the anti-amyloidogenic effect of molecular chaperone artemin on α-synuclein. As the concentration of artemin was increased up to 4 μg/ml, a decrease in fibril formation of α-synuclein was observed using ThT fluorescence and congo red assay. TEM images also demonstrated a reduction in fibrils in the presence of artemin. The secondary structure of α-synuclein was similar to its native form prior to fibrillation when incubated with artemin. A cell-based assay has shown that artemin inhibits α-synuclein aggregation and reduce cytoxicity, apotosis and ROS production. Our results revealed that artemin has efficient chaperon activity for preventing α-synuclein fibril formation and toxicity.


2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Samra Hasanbašić ◽  
Alma Jahić ◽  
Selma Berbić ◽  
Magda Tušek Žnidarič ◽  
Eva Žerovnik

Amyloid fibril formation is a shared property of all proteins; therefore, model proteins can be used to study this process. We measured protein aggregation of the model amyloid-forming protein stefin B in the presence and absence of several antioxidants. Amyloid fibril formation by stefin B was routinely induced at pH 5 and 10% TFE, at room temperature. The effects of antioxidants NAC, vitamin C, vitamin E, and the three polyphenols resveratrol, quercetin, and curcumin on the kinetics of fibril formation were followed using ThT fluorescence. Concomitantly, the morphology and amount of the aggregates and fibrils were checked by transmission electron microscopy (TEM). The concentration of the antioxidants was varied, and it was observed that different modes of action apply at low or high concentrations relative to the binding constant. In order to obtain more insight into the possible mode of binding, docking of NAC, vitamin C, and all three polyphenols was done to the monomeric form of stefin B.


Author(s):  
D.M. Vanderwalker

There is a fundamental interest in electrochemical fusion of deuterium in palladium and titanium since its supposed discovery by Fleischmann and Pons. Their calorimetric experiments reveal that a large quantity of heat is released by Pd after hours in a cell, suggesting fusion occurs. They cannot explain fusion by force arguments, nor can it be an exothermic reaction on the formation of deuterides because a smaller quantity of heat is released. This study examines reactions of deuterium in titanium.Both iodide titanium and 99% pure titanium samples were encapsulated in vacuum tubes, annealed for 2h at 800 °C. The Ti foils were charged with deuterium in a D2SO4 D2O solution at a potential of .45V with respect to a calomel reference junction. Samples were ion beam thinned for transmission electron microscopy. The TEM was performed on the JEOL 200CX.The structure of D charged titanium is α-Ti with hexagonal and fee deuterides.


Nanomaterials ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 1463 ◽  
Author(s):  
Vishma Pratap Sur ◽  
Marketa Kominkova ◽  
Zaneta Buchtova ◽  
Kristyna Dolezelikova ◽  
Ondrej Zitka ◽  
...  

The physical and chemical synthesis methods of quantum dots (QDs) are generally unfavorable for biological applications. To overcome this limitation, the development of a novel “green” route to produce highly-fluorescent CdSe QDs constitutes a promising substitute approach. In the present work, CdSe QDs were biosynthesized in yeast Saccharomyces cerevisiae using a novel method, where we showed for the first time that the concentration of tryptone highly affects the synthesis process. The optimum concentration of tryptone was found to be 25 g/L for the highest yield. Different methods were used to optimize the QD extraction from yeast, and the best method was found to be by denaturation at 80 °C along with an ultrasound needle. Multiple physical characterizations including transmission electron microscopy (TEM), dynamic light scattering (DLS), energy-dispersive X-ray spectroscopy (EDX), and spectrophotometry confirmed the optical features size and shape distribution of the QDs. We showed that the novel conjugate of the CdSe QDs and a cell-penetrating peptide (hecate) can detect bacterial cells very efficiently under a fluorescent microscope. The conjugate also showed strong antibacterial activity against vancomycin-resistant Staphylococcus aureus (VRSA), methicillin-resistant Staphylococcus aureus (MRSA), and Escherichia coli, which may help us to cope with the problem of rising antibiotic resistance.


2021 ◽  
Vol 22 (3) ◽  
pp. 1285
Author(s):  
Seong Soon Kim ◽  
Hyemin Kan ◽  
Kyu-Seok Hwang ◽  
Jung Yoon Yang ◽  
Yuji Son ◽  
...  

Epilepsy is one of the most common neurological disorders, and it is characterized by spontaneous seizures. In a previous study, we identified 4-(2-chloro-4-fluorobenzyl)-3-(2-thienyl)-1,2,4-oxadiazol-5(4H)-one (GM-90432) as a novel anti-epileptic agent in chemically- or genetically-induced epileptic zebrafish and mouse models. In this study, we investigated the anti-epileptic effects of GM-90432 through neurochemical profiling-based approach to understand the neuroprotective mechanism in a pentylenetetrazole (PTZ)-induced epileptic seizure zebrafish model. GM-90432 effectively improved PTZ-induced epileptic behaviors via upregulation of 5-hydroxytryptamine, 17-β-estradiol, dihydrotestosterone, progesterone, 5α -dihydroprogesterone, and allopregnanolone levels, and downregulation of normetanephrine, gamma-aminobutyric acid, and cortisol levels in brain tissue. GM-90432 also had a protective effect against PTZ-induced oxidative stress and zebrafish death, suggesting that it exhibits biphasic neuroprotective effects via scavenging of reactive oxygen species and anti-epileptic activities in a zebrafish model. In conclusion, our results suggest that neurochemical profiling study could be used to better understand of anti-epileptic mechanism of GM-90432, potentially leading to new drug discovery and development of anti-seizure agents.


1980 ◽  
Vol 1 ◽  
Author(s):  
S.W. Chiang ◽  
Y.S. Liu ◽  
R.F. Reihl

ABSTRACTHigh-dose ion implantation (1017 ions-cm−2) of C+, N+, and O+ at 50 KeV into silicon followed by pulsed laser annealing at 1.06 μm was studied. Formation of SiC, Si3N4, and SiO2 has been observed and investigated using Transmission Electron Microscopy (TEM) and Differential Fourier-Transform Infrared (FT-IR) Spectroscopy. Furthermore, in N+-implanted and laser-annealed silicon samples, we have observed a cell-like structure which has been identified to be spheroidal polycrystalline silicon formed by the rapid laser irradiation.


Author(s):  
Li Ming ◽  
Wu Xiufeng

Abstract ZrSi/ZrC nanocomposites have stable high-temperature properties, where conventional materials cannot meet increasingly demanding high-temperature environments. In this paper, the microstructure and electrochemical reduction mechanism of ZrSi/ZrC nanocomposites have been studied. A mixture of ZrSiO4 and carbon black powder was processed using ball grinding, sheet pressing, and sintering, and cylindrically-sintered sheet was prepared as the cathode for the electrolytic work. A high purity graphite rod was utilized as the anode.The microstructure of the electrolytic product was characterized and analyzed using X-ray diffraction, scanning electron microscopy equipped with energy-dispersive X-ray spectroscopy, and transmission electron microscopy. The experimental results showed that the diameter of the as-synthesized ZrSi/ ZrC fibers typically range between 100-400 nm when produced by the electrolysis of sintered pellets in equimolar CaCl2-NaCl molten salt at 850°C with a cell voltage of 2.8 V for 20 h under an argon atmosphere. The nanofibers were formed in core-shell microstructures that overlap and grow.


1985 ◽  
Vol 100 (6) ◽  
pp. 1922-1929 ◽  
Author(s):  
B F McEwen ◽  
W J Arion

Pathogenic staphylococci secrete a number of exotoxins, including alpha-toxin. alpha-Toxin induces lysis of erythrocytes and liposomes when its 3S protein monomers associate with the lipid bilayer and form a hexomeric transmembrane channel 3 nm in diameter. We have used alpha-toxin to render rat hepatocytes 93-100% permeable to trypan blue with a lactate dehydrogenase leakage less than or equal to 22%. Treatment conditions included incubation for 5-10 min at 37 degrees C and pH 7.0 with an alpha-toxin concentration of 4-35 human hemolytic U/ml and a cell concentration of 13-21 mg dry wt/ml. Scanning electron microscopy revealed signs of swelling in the treated hepatocytes, but there were no large lesions or gross damage to the cell surface. Transmission electron microscopy indicated that the nucleus, mitochondria, and cytoplasm were similar in control and treated cells and both had large regions of well-defined lamellar rough endoplasmic reticulum. Comparisons of the mannose-6-phosphatase and glucose-6-phosphatase activities demonstrated that 5-10 U/ml alpha-toxin rendered cells freely permeable to glucose-6-phosphate, while substantially preserving the selective permeability of the membranes of the endoplasmic reticulum and the functionality of the glucose-6-phosphatase system. Thus, alpha-toxin appears to have significant potential as a means to induce selective permeability to small ions. It should make possible the study of a variety of cellular functions in situ.


2007 ◽  
Vol 73 (17) ◽  
pp. 5566-5573 ◽  
Author(s):  
Rok Kostanjšek ◽  
Jasna Štrus ◽  
Gorazd Avguštin

ABSTRACT Pointed, rod-shaped bacteria colonizing the cuticular surface of the hindgut of the terrestrial isopod crustacean Porcellio scaber (Crustacea: Isopoda) were investigated by comparative 16S rRNA gene sequence analysis and electron microscopy. The results of phylogenetic analysis, and the absence of a cell wall, affiliated these bacteria with the class Mollicutes, within which they represent a novel and deeply branched lineage, sharing less than 82.6% sequence similarity to known Mollicutes. The lineage has been positioned as a sister group to the clade comprising the Spiroplasma group, the Mycoplasma pneumoniae group, and the Mycoplasma hominis group. The specific signature sequence was identified and used as a probe in in situ hybridization, which confirmed that the retrieved sequences originate from the attached rod-shaped bacteria from the hindgut of P. scaber and made it possible to detect these bacteria in their natural environment. Scanning and transmission electron microscopy revealed a spherically shaped structure at the tapered end of the rod-shaped bacteria, enabling their specific and exclusive attachment to the tip of the cuticular spines on the inner surface of the gut. Specific adaptation to the gut environment, as well as phylogenetic positioning, indicate the long-term association and probable coevolution of the bacteria and the host. Taking into account their pointed, rod-shaped morphology and their phylogenetic position, the name “Candidatus Bacilloplasma” has been proposed for this new lineage of bacteria specifically associated with the gut surface of P. scaber.


2021 ◽  
Vol 17 (10) ◽  
pp. 1972-1983
Author(s):  
Yi Zhang ◽  
Qing Jiang ◽  
Xinyi Liu ◽  
Liping Peng ◽  
Xinyi Tang ◽  
...  

To discuss the effect of hydrophobic groups of a polymer on the structural properties and function of polymer nanoparticles (NPs), we grafted chenodeoxycholic acid (CDCA) with pullulan (PU) to form hydrophobically modified PU (PUC). Three PUC polymers, namely, PUC-1, PUC-2, and PUC-3, with different degrees of substitution were designed by changing the feed ratio of CDCA and PU. 1H-NMR spectra showed that the PUC polymer was successfully synthesized, and the degrees of hydrophobic substitution for PUC-1, PUC-2, and PUC-3 were calculated to be 10.66%, 13.92%, and 16.94%, respectively. The PUC NPs were prepared by the dialysis method and were shown to be uniformly spherical by transmission electron microscopy (TEM). The average sizes were about (220±10) nm, (203±7) nm, and (163±6) nm under dynamic light scattering (DLS) for PUC-1 NPs, PUC-2 NPs, and PUC-3 NPs, respectively. Drug release experiments showed that the three PUC/DOX NPs exhibited good sustained release. At 48 h, the IC50 of doxorubicin in inhibiting colon cancer HCT116 cells was 0.0904 μg/mL. A cell study showed that PUC-3/DOX NPs had the highest uptake efficiency by HCT116 cells with the most cytotoxicity and inhibited the migration of HCT116 cells with the highest efficiency. The structural properties and function of polymer NPs were closely related to the hydrophobic groups in the polymer, and NPs with higher hydrophobicity showed a smaller size, higher drug capacity, and greater cell efficiency.


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