Proteins MiaA and MiaB catalyze sequential isopentenylation and methylthiolation, respectively, of adenosine residue in 37th position of tRNAXXA. The mia mutations were recently shown by us to affect secondary metabolism and morphology of Streptomyces. However, it remained unknown as to whether both or one of the aforementioned modifications is critical for colony development and antibiotic production. Here, we addressed this issue through analysis of Streptomyces albus J1074 strains carrying double miaAmiaB knockout or extra copy of miaB gene. The double mutant differed from wild-type and miaA-minus strains in severity of morphological defects, growth dynamics, and secondary metabolism. Introduction of extra copy of miaB gene into miaA mutant restored aerial mycelium formation to the latter on certain solid media. Hence, miaB gene might be involved in tRNA thiomethylation in the absence of miaA; either MiaA- or MiaB-mediated modification appears to be enough to support normal metabolic and morphological processes in Streptomyces.

• MeSH
• alkyltransferasy a aryltransferasy genetika   MeSH
• antibakteriální látky biosyntéza   MeSH
• bakteriální geny genetika   MeSH
• bakteriální proteiny genetika   MeSH
• fenotyp * MeSH
• genetická transkripce MeSH
• genetické testování metody   MeSH
• mutace MeSH
• peroxid vodíku farmakologie   MeSH
• posttranskripční úpravy RNA * MeSH
• RNA transferová metabolismus   MeSH
• sekundární metabolismus účinky léků   genetika   MeSH
• Streptomyces účinky léků   genetika   růst a vývoj   metabolismus   MeSH
• sulfurtransferasy genetika   MeSH
• Publikační typ
• časopisecké články MeSH

Lipid peroxidation is a major deleterious effect caused by oxidative stress. It is involved in various diseases such as atherosclerosis, rheumatoid arthritis and neurodegenerative diseases. In order to inhibit lipid peroxidation, antioxidants must efficiently scavenge free radicals and penetrate inside biological membranes. Lipocarbazole has recently been shown to be a powerful antioxidant in solution. Here, we show its powerful capacity as lipid peroxidation inhibitor. Its mechanism of action is rationalized based on molecular dynamics simulations on a biomembrane model, quantum calculations and experimental evaluation. The role of the lipocarbazole side chain is particularly highlighted as a critical chemical feature responsible for its antioxidant activity.

• MeSH
• antioxidancia chemie   metabolismus   MeSH
• karbazoly chemie   metabolismus   MeSH
• kvantová teorie MeSH
• mastné kyseliny chemie   metabolismus   MeSH
• simulace molekulární dynamiky MeSH
• termodynamika MeSH
• unilamelární lipozómy chemie   metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Analyzing mixture toxicity requires an in-depth understanding of the mechanisms of action of its individual components. Substances with the same target organ, same toxic effect and same mode of action (MoA) are believed to cause additive effects, whereas substances with different MoAs are assumed to act independently. Here, we tested 2 triazole fungicides, propiconazole, and tebuconazole (Te), for individual and combined effects on liver toxicity-related endpoints. Both triazoles are proposed to belong to the same cumulative assessment group and are therefore thought to display similar and additive behavior. Our data show that Te is an antagonist of the constitutive androstane receptor (CAR) in rats and humans, while propiconazole is an agonist of this receptor. Both substances activate the pregnane X-receptor (PXR) and further induce mRNA expression of CYP3A4. CYP3A4 enzyme activity, however, is inhibited by propiconazole. For common targets of PXR and CAR, the activation of PXR by Te overrides CAR inhibition. In summary, propiconazole and Te affect different hepatotoxicity-relevant cellular targets and, depending on the individual endpoint analyzed, act via similar or dissimilar mechanisms. The use of molecular data based on research in human cell systems extends the picture to refine cumulative assessment group grouping and substantially contributes to the understanding of mixture effects of chemicals in biological systems.

• MeSH
• buněčné kultury MeSH
• hepatocyty účinky léků   metabolismus   MeSH
• krysa rodu rattus MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• pregnanový X receptor agonisté   genetika   MeSH
• průmyslové fungicidy farmakologie   MeSH
• receptory cytoplazmatické a nukleární agonisté   antagonisté a inhibitory   genetika   MeSH
• simulace molekulového dockingu MeSH
• substrátová specifita MeSH
• synergismus léků MeSH
• systém (enzymů) cytochromů P-450 genetika   metabolismus   MeSH
• transfekce MeSH
• triazoly farmakologie   MeSH
• viabilita buněk účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• Publikační typ
• abstrakty MeSH

• MeSH
• alkaloidy biosyntéza   MeSH
• Bacteria genetika   metabolismus   MeSH
• biosyntéza peptidů nezávislá na nukleových kyselinách MeSH
• databáze genetické MeSH
• genetické markery MeSH
• houby genetika   metabolismus   MeSH
• metagenom MeSH
• mezinárodní spolupráce MeSH
• multigenová rodina * MeSH
• peptidy metabolismus   MeSH
• polyketidy metabolismus   MeSH
• polysacharidy biosyntéza   MeSH
• proteosyntéza * MeSH
• rostliny genetika   metabolismus   MeSH
• terminologie jako téma MeSH
• terpeny metabolismus   MeSH
• výpočetní biologie normy   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH