As compounds of natural origin enter human body, it is necessary to investigate their possible interactions with the metabolism of drugs and xenobiotics in general, namely with the cytochrome P450 (CYP) system. Phytic acid (myo-inositol hexaphosphoric acid, IP6) is mainly present in plants but is also an endogenous compound present in mammalian cells and tissues. It has been shown to exhibit protective effect in many pathological conditions. For this paper, its interaction with CYPs was studied using human liver microsomes, primary human hepatocytes, the HepG2 cell line, and molecular docking. Docking experiments and absorption spectra demonstrated the weak ability of IP6 to interact in the heme active site of CYP1A. Molecular docking suggested that IP6 preferentially binds to the protein surface, whereas binding to the active site of CYP1A2 was found to be less probable. Subsequently, we investigated the ability of IP6 to modulate the metabolism of xenobiotics for both the mRNA expression and enzymatic activity of CYP1A enzymes. Our findings revealed that IP6 can slightly modulate the mRNA levels and enzyme activity of CYP1A. However, thanks to the relatively weak interactions of IP6 with CYPs, the chances of the mechanisms of clinically important drug-drug interactions involving IP6 are low.
- MeSH
- kyselina fytová * MeSH
- lidé MeSH
- messenger RNA MeSH
- savci MeSH
- simulace molekulového dockingu MeSH
- systém (enzymů) cytochromů P-450 MeSH
- xenobiotika * MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Kyselina fytová (IP6) je nejhojněji se vyskytující inositolfosfát v přírodě, přítomný především v rostlinách, ale také v savčích buňkách. V současnosti je široce studována pro své rozmanité vlastnosti. Má schopnost vázat polyvalentní kationty, což bylo dříve považováno za nevýhodu ve spojitosti se sníženou dostupností minerálů z potravy. Na druhé straně jí tato struktura umožňuje funkci přírodního antioxidantu. Protektivní účinky kyseliny fytové byly popsány u patologických stavů včetně neurodegenerativních onemocnění, urolithiázy a rovněž zhoubného bujení.
Phytic acid (IP6, inositol hexaphosphate) is the most abundant inositol phosphate in nature. It is present mostly in plants but it has ben found also in mammalian cells. IP6 is extensively studied because of enormous variety of its properties. It binds polyvalent cations which was formerly considered as disadvantage responsible for lowered bioavailability of minerals in food. On the other hand, its stucture allows it to act as a natural antioxidant. Protective effect of IP6 has been found in varoius pathologies incl. neuorodegenerative disorders, urolithiasis as well as in malignancies.
- MeSH
- kyselina fytová * chemie škodlivé účinky terapeutické užití MeSH
- lidé MeSH
- protinádorové látky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- MeSH
- alkaloidy chemie škodlivé účinky MeSH
- bezpečnost potravin MeSH
- fytonutrienty * analýza chemie škodlivé účinky MeSH
- kyanidy chemie škodlivé účinky MeSH
- kyselina fytová chemie škodlivé účinky MeSH
- lektiny chemie škodlivé účinky MeSH
- mykotoxiny chemie škodlivé účinky MeSH
- otrava houbami MeSH
- taniny analýza chemie škodlivé účinky MeSH
- vitaminy antagonisté a inhibitory MeSH
- živiny antagonisté a inhibitory MeSH
- Publikační typ
- přehledy MeSH
Inositol hexaphosphate (IP6), also known as phytic acid, has been shown to exhibit anticancer effects in a number of preclinical tumor models. IP6 decreases proliferation by arresting cells in the G0/G1 phase, inhibits iron-mediated oxidative reactions, enhances differentiation and stimulates apoptosis. The present study attempted to characterize the effect of IP6 on the migration and adhesion of colon cancer SW620 cells. IP6 was assessed at concentrations of 0.2 and 1 mM during 12, 24 and 48 h of exposure. Migration ability was measured with the real-time xCELLigence Real-Time Cell Analyzer Dual Purpose system. The expression of mRNA and proteins involved in migration and cancer progression [epithelial cell adhesion molecule, intercellular adhesion molecule-1, β-catenin, N-cadherin, E-cadherin, matrix metalloproteinase (MMP)-2 and MMP-9] was determined by reverse transcription-quantitative polymerase chain reaction and western blot analysis. The changes in the expression and subcellular localization of E-cadherin were determined by indirect immunofluorescence. IP6 induced a decrease in the migration ability of the tested SW620 cell line. IP6-treated cells also showed decreased expression of N-cadherin, increased levels of E-cadherin and decreased expression of MMP-2 and MMP-9. These results indicated that IP6 has potential to modulate the migration ability and expression of markers associated with invasion in SW620 cells; however, further analysis is necessary to obtain a detailed understanding of the mechanism of action.
- MeSH
- buněčná adheze účinky léků MeSH
- invazivní růst nádoru prevence a kontrola MeSH
- kolorektální nádory farmakoterapie patologie MeSH
- kyselina fytová farmakologie terapeutické užití MeSH
- lidé MeSH
- nádorové biomarkery metabolismus MeSH
- nádorové buněčné linie MeSH
- pohyb buněk účinky léků MeSH
- progrese nemoci MeSH
- protinádorové látky farmakologie terapeutické užití MeSH
- screeningové testy protinádorových léčiv MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Even though the majority of knowledge about phospholipids comes from their cytoplasmic functions, in the last decade, it has been shown that nuclear phospholipids and their building blocks, inositol phosphates, have many important roles in the cell nucleus. There are clear connections of phospholipids with the regulation of gene expression and chromatin biology, however, this review focuses on less known functions of nuclear phospholipids in connection with the epigenome regulation. In particular, we highlight the roles of nuclear phospholipids and inositol phosphates that involve histone modifications, such as acetylation or methylation, tightly connected with the cell physiology. This demonstrates the importance of nuclear phospholipids in the regulation of cellular processes, and should encourage further research of nuclear phospholipids and inositol phosphates.
- MeSH
- chromatin chemie metabolismus MeSH
- epigeneze genetická * genetika MeSH
- fosfolipidy chemie metabolismus MeSH
- inositolfosfáty chemie metabolismus MeSH
- lidé MeSH
- molekulární struktura MeSH
- regulace genové exprese MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Xanomeline (3-(Hexyloxy)-4-(1-methyl-1,2,5,6-tetrahydropyridin-3-yl)-1,2,5-thiadiazole) is a muscarinic agonist that is considered to be functionally selective for the M1/M4 receptor subtypes. Part of xanomeline binding is resistant to washing. Wash-resistant xanomeline activates muscarinic receptors persistently, except for the M5 subtype. Mutation of leucine 6.46 to isoleucine at M1 or M4 receptors abolished persistent activation by wash-resistant xanomeline. Reciprocal mutation of isoleucine 6.46 to leucine at the M5 receptor made it sensitive to activation by wash-resistant xanomeline. Lowering of membrane cholesterol made M1 and M4 mutants and M5 wild type receptors sensitive to activation by wash-resistant xanomeline. Molecular docking revealed a cholesterol binding site in the groove between transmembrane helices 6 and 7. Molecular dynamics showed that interaction of cholesterol with this binding site attenuates receptor activation. We hypothesize that differences in cholesterol binding to this site between muscarinic receptor subtypes may constitute the basis for xanomeline apparent functional selectivity and may have notable therapeutic implications. Differences in receptor-membrane interactions, rather than in agonist-receptor interactions, represent a novel possibility to achieve pharmacological selectivity. Our findings may be applicable to other G protein coupled receptors.
- MeSH
- agonisté muskarinových receptorů farmakokinetika MeSH
- buněčná membrána účinky léků metabolismus MeSH
- CHO buňky cytologie MeSH
- cholesterol metabolismus MeSH
- Cricetulus MeSH
- inositolfosfáty metabolismus MeSH
- magnetická rezonanční spektroskopie MeSH
- molekulární modely MeSH
- průtoková cytometrie MeSH
- pyridiny farmakokinetika MeSH
- radioligandová zkouška MeSH
- receptory muskarinové genetika metabolismus MeSH
- simulace molekulového dockingu MeSH
- thiadiazoly farmakokinetika MeSH
- tritium farmakokinetika MeSH
- vápník metabolismus MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- anovulace farmakoterapie MeSH
- hyperandrogenismus farmakoterapie MeSH
- hyperinzulinismus farmakoterapie MeSH
- inositol-1,4,5-trisfosfát aplikace a dávkování farmakologie MeSH
- lidé MeSH
- metformin aplikace a dávkování farmakologie MeSH
- syndrom polycystických ovarií * farmakoterapie MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
The article reports on the main antinutritional compounds in legumes which have a unique nutritive value, especially for vegetarians. Besides a high amount of proteins, saccharides, dietary fibres, minerals and vitamins, the legumes contain a wide range of negative bioactive compounds, such as allergens, protease inhibitors, lectins, non-proteinogenic amino acids, α-galactooligosaccharides, cyanogen glycosides, phytates, phenolic compounds and alkaloids. This review aims to show the adverse effect of antinutritional compounds in legumes on human health and call attention to the risk of consummation of legume seeds without an adequate inactivation of dangerous substances.
- Klíčová slova
- antinutriční látky,
- MeSH
- alergeny MeSH
- alkaloidy MeSH
- amylasy antagonisté a inhibitory MeSH
- bezpečnost potravin MeSH
- dietní proteiny klasifikace škodlivé účinky MeSH
- dietní sacharidy škodlivé účinky MeSH
- Fabaceae * chemie škodlivé účinky MeSH
- fenoly škodlivé účinky MeSH
- fyziologie výživy MeSH
- glykosidy klasifikace škodlivé účinky MeSH
- inhibitory proteas MeSH
- kyselina fytová analogy a deriváty MeSH
- lektiny škodlivé účinky MeSH
- lidé MeSH
- ovoce * chemie škodlivé účinky MeSH
- průmysl zpracování potravin MeSH
- Check Tag
- lidé MeSH
- MeSH
- fosforečnany vápenaté chemie metabolismus MeSH
- kaménky metabolismus MeSH
- kyselina fytová chemie metabolismus MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- dopisy MeSH
- práce podpořená grantem MeSH
