Parkinson's disease is characterized by the selective death of dopaminergic neurons in the midbrain and accumulation of amyloid fibrils composed of α-synuclein (αSyn). Current treatment involves approaches that compensate the death of dopaminergic neurons by increasing the dopamine levels in remaining cells. However, dopamine can interact with αSyn and produce oligomeric species which were reported to be toxic in many models. We studied formation of dopamine-induced αSyn oligomers and their effect on the αSyn aggregation. Using the Thioflavin T kinetic assay, we have shown that small oligomers efficiently inhibit αSyn fibrillization by binding to fibril ends and blocking the elongation. Moreover, all the fractions of oligomer species proved to be nontoxic in the differentiated SH-SY5Y cell model and showed negligible neurotoxicity on isolated rat synaptosomes. The observed inhibition is an important insight in understanding of dopamine-enhancing therapy on Parkinson's disease progression and explains the absence of pathology enhancement.
- MeSH
- alfa-synuklein metabolismus MeSH
- amyloid metabolismus MeSH
- dopamin chemie MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- neuroblastom * MeSH
- Parkinsonova nemoc * metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
On-line SPE HPLC method using nanofibrous sorbents for the extraction and determination of resveratrol in wine was developed and validated. Different types of nanofibrous and microfibrous polymers were tested and compared with commercial monolithic C18 sorbent. Polyamide and polyacrylonitrile nanofibers and composite materials composed of respective polycaprolactone and poly(vinylidene difluoride) nanofibers at microfibrous scaffold were included among tested materials. Two different polycaprolactone-based materials were prepared and their effect on the extraction properties studied. Alternatively, dopamine-coated polycaprolactone fibers were also used. Poly(vinylidene difluoride) nanofibers/polycaprolactone microfibers composite was found as the most effective sorbent and utilized for the method validation. Resveratrol in red wine was determined using our validated on-line SPE HPLC method.
Seven retention models have been selected to describe a dual-retention behavior of ten dopamine-related compounds on polymer-based monolithic stationary phase with zwitterion sulfobetaine functionality. Regression quality, as well as a statistical significance of individual regression parameters, have been evaluated. Better regression performance showed two four-parameter models when compared to three-parameter models. On the other hand, limited number of experimental points disqualified statistical robustness of four-parameter models. Among three-parameter models, retention description introduced by Horváth and Liang provided comparable quality of regression at significantly improved robustness. Multivariate analysis of the best three-parameter models provided the description of physicochemical properties of dopamine precursors and metabolites. Principal component analysis and logistic regression allowed structural characterization of dopamine-related compounds based solely on regression parameters extracted from an isocratic elution data. Both polarity and type of functional groups has been correctly assigned for 3-methoxytyramine that has not been part of an evaluation study. Among applied dual-retention models, Horváth´s model, initially developed to describe a retention of ionic compounds on nonpolar stationary phases, provided robust regression of experimental data and allowed an extraction of structural characteristics of dopamine-related compounds.
Sodium hyaluronate (HA) was associated with dopamine (DPA) and introduced as a coating for maghemite (γ-Fe(2)O(3)) nanoparticles obtained by the coprecipitation of iron(II) and iron(III) chlorides and oxidation with sodium hypochlorite. The effects of the DPA anchorage of HA on the γ-Fe(2)O(3) surface on the physicochemical properties of the resulting colloids were investigated. Nanoparticles coated at three different DPA-HA/γ-Fe(2)O(3) and DPA/HA ratios were chosen for experiments with rat bone marrow mesenchymal stem cells and human chondrocytes. The nanoparticles were internalized into rat bone marrow mesenchymal stem cells via endocytosis as confirmed by Prussian Blue staining. The efficiency of mesenchymal stem cell labeling was analyzed. From among the investigated samples, efficient cell labeling was achieved by using DPA-HA-γ-Fe(2)O(3) nanoparticles with DPA-HA/γ-Fe(2)O(3) = 0.45 (weight/ weight) and DPA/HA = 0.038 (weight/weight) ratios. The particles were used as a contrast agent in magnetic resonance imaging for the labeling and visualization of cells.
- MeSH
- biokompatibilní potahované materiály chemie MeSH
- buněčná diferenciace MeSH
- chondrocyty cytologie MeSH
- dopamin chemie MeSH
- endocytóza MeSH
- ferrokyanidy MeSH
- kontrastní látky diagnostické užití MeSH
- krysa rodu rattus MeSH
- kultivované buňky MeSH
- kyselina hyaluronová chemie MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- magnetické nanočástice chemie diagnostické užití ultrastruktura MeSH
- mezenchymální kmenové buňky cytologie účinky léků MeSH
- nanomedicína MeSH
- transmisní elektronová mikroskopie MeSH
- velikost částic MeSH
- viabilita buněk MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Parkinsonova choroba patrí medzi najčastejšie sa vyskytujúce neurodegeneratívne ochorenie so závažnými socioekonomickými dôsledkami. Z hľadiska súčasných poznatkov ide o ochorenie nevyliečiteľné, avšak včasnou diagnostikou a vhodne zahájenou liečbou sa dá prispieť k zlepšeniu kvality života pacienta. Príčina vzniku Parkinsonovej choroby nie je dodnes presne známa. V súčasnosti sa množia dôkazy podporujúce teóriu, že oxidatívny stres a mitochondriálna dysfunkcia môžu mať zásadný význam v patogenéze ochorenia. Výskum mechanizmov zahrnutých v zložitom procese neurodogenerácie PCh by mohla priniesť možnosť identifikácie rizikových a presymptomatických jedincov, ako aj identifikovanie terapeutického cieľa a následnej neuroprotektívnej liečby.
Parkinson's disease is the most common neurodegenerative disorder, with serious socio-economic consequences. At present the disorder appears incurable, but well-timed diagnostics and appropriate therapy can improve the quality of life for those who suffer from it. Recent research appears to support a hypothesis that oxidative damage and mitochondrial dysfunction may play a primary role in the pathogenesis of PD. Further investigation of the mechanisms implicated in the complex process of neurodegeneration may result in the possibility of identifying individuals at risk and presymptomatic patients, and also determining proper therapeutic targets and subsequent neuroprotective treatments.
- MeSH
- apoptóza genetika imunologie MeSH
- dopamin chemie metabolismus škodlivé účinky MeSH
- kyselina močová krev metabolismus MeSH
- lidé MeSH
- mitochondriální DNA izolace a purifikace MeSH
- mitochondriální nemoci diagnóza etiologie genetika MeSH
- mutace fyziologie genetika imunologie MeSH
- neurodegenerativní nemoci etiologie farmakoterapie MeSH
- neurony chemie metabolismus účinky léků MeSH
- neuroprotektivní látky metabolismus terapeutické užití MeSH
- oxidační stres fyziologie genetika imunologie MeSH
- Parkinsonova nemoc diagnóza etiologie farmakoterapie MeSH
- poruchy metabolismu vápníku etiologie genetika MeSH
- poruchy metabolismu železa etiologie genetika MeSH
- stárnutí fyziologie genetika imunologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Lastovičník väčší podobne ako iné rastliny z čeľade Papaveraceae produkuje benzylizochinolínové alkaloidy, predovšetkým benzofenantridíny. Polyfenoloxidáza (PPO) je pravdepodobne zapojená do tvorby dopamínu, ktorý je jedným z prekurzorov norkoklaurínu, prvého intermediátu s benzylizochinolínovou štruktúrou. V rámci práce bolo zistené, že PPO prítomná v latexe lastovičníka je lokalizovaná v organelách, ktoré slúžia k uskladneniu alkaloidov (tzv. 1000 g organely). Enzým bol purifikovaný afinitnou chromatografiou do elektroforetickej homogenity, má relatívnu molekulovú hmotnosť približne 65 kDa a vykazuje dve aktivity – monofenolázovú a difenolázovú. Použitím polymerázovej reťazovej reakcie sa podarilo amplifikovať časť génu PPO z oblasti aktívneho miesta.
Greater celandine, similarly as other plants of the family Papaveraceae, produces benzylisoquinoline alkaloids, primarily benzophenanthridines. Polyphenoloxidase (PPO) is most probably involved in the formation of dopamine, which is one of the precursors of norcoclaurine, the first intermediate with the benzylisoquinoline structure. This study has revealed that PPO present in the latex of greater celandine is localized in the organelles, which serve to store alkaloids (the so-called 1000 g organelles). The enzyme was purified by means of affinity chromatography into electrophoretic homogeneity. It possesses a relative molecular mass of approximately 65 kDa and exerts two activities, the monophenolase and diphenolase ones. With the use of a polymerase chain reaction, it was possible to amplify a part of the PPO gene from the region of the active site.
- MeSH
- alkaloidy chemie izolace a purifikace MeSH
- Chelidonium chemie MeSH
- chromatografie afinitní metody využití MeSH
- dopamin chemie MeSH
- elektroforéza v polyakrylamidovém gelu metody využití MeSH
- fenoly chemie MeSH
- financování organizované MeSH
- latex chemie MeSH
- lidé MeSH
- polymerázová řetězová reakce metody využití MeSH
- Check Tag
- lidé MeSH
- MeSH
- dítě MeSH
- dopamin-beta-hydroxylasa fyziologie chemie MeSH
- dopamin genetika chemie MeSH
- hyperkinetická porucha genetika MeSH
- jednonukleotidový polymorfismus genetika účinky léků MeSH
- krevní plazma fyziologie MeSH
- lidé MeSH
- noradrenalin genetika chemie MeSH
- polymorfismus genetický genetika MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
The influence of side-chain structure on the mode of reaction of ortho-quinone amines has been investigated with a view, ultimately, to developing potential methods of therapeutic intervention by manipulating the early stages of melanogenesis. Four N-substituted dopamine derivatives have been prepared and quinone formation studied using pulse radiolysis and tyrosinase-oximetry. Ortho-quinones with an amide or urea side chain were relatively stable, although evidence for slow formation of isomeric para-quinomethanes was observed. A thiourea derivative cyclized fairly rapidly (k = 1.7/s) to a product containing a seven-membered ring, whereas a related amidine gave more rapidly (k approximately 2.5 x 10(2)/s) a stable spirocyclic product. The results suggest that cyclization of amides, ureas and carbamates (NHCO-X; X = R, NHR or OR) does not occur and is not, therefore, a viable approach to the formation of tyrosinase-activated antimelanoma prodrugs. It is also concluded that for N-acetyldopamine spontaneous ortho-quinone to para-quinomethane isomerization is slow.
- MeSH
- Agaricus enzymologie MeSH
- antitumorózní látky chemie terapeutické užití MeSH
- dopamin analogy a deriváty chemie MeSH
- financování organizované MeSH
- fungální proteiny chemie MeSH
- isomerie MeSH
- melaniny chemická syntéza chemie MeSH
- melanom enzymologie farmakoterapie MeSH
- molekulární struktura MeSH
- nádorové proteiny chemie MeSH
- oxidace-redukce MeSH
- prekurzory léčiv chemie MeSH
- tyrosinasa chemie MeSH
