Ellipticine and benzo(a)pyrene increase their own metabolic activation via modulation of expression and enzymatic activity of cytochromes P450 1A1 and 1A2

Two compounds known to covalently bind to DNA after their activation with cytochromes P450 (CYPs), carcinogenic benzo(a)pyrene (BaP) and an antineoplastic agent ellipticine, were investigated for their potential to induce CYP and NADPH:CYP reductase (POR) enzymes in rodent livers, the main target organ for DNA adduct formation. Two animal models were used in the study: (i) rats as animals mimicking the fate of ellipticine in humans and (ii) mice, especially wild-type (WT) and hepatic POR null (HRN™) mouse lines. Ellipticine and BaP induce expression of CYP1A enzymes in livers of experimental models, which leads to increase in their enzymatic activity. In addition, both compounds are capable of generating DNA adducts, predominantly in livers of studied organisms. As determined by 32P postlabelling analysis, levels of ellipticine-derived DNA adducts formed in vivo in the livers of HRN™ mice were reduced (by up to 65%) relative to levels in WT mice, indicating that POR mediated CYP enzyme activity is important for the activation of ellipticine. In contrast to these results, 6.4 fold higher DNA binding of BaP was observed in the livers of HRN™ mice than in WT mice. This finding suggests a detoxication role of CYP1A in BaP metabolism in vivo. In in vitro experiments, DNA adduct formation in calf thymus DNA was up to 25 fold higher in incubations of ellipticine or BaP with microsomes from pretreated animals than with controls. This stimulation effect was attributed to induction of CYP1A1/2 enzymes, which are responsible for oxidative activation of both compounds to the metabolites generating major DNA adducts in vitro. Taken together, these results demonstrate that by inducing CYP1A1/2, ellipticine and BaP modulate their own enzymatic metabolic activation and detoxication, thereby modulating their either pharmacological (ellipticine) and/or genotoxic potential (both compounds)

Stucture of phosphoenolpyruvate carboxylase from maize leaves

AbstractPhosphoenolpyruvate carboxylase (PEPC) from maize leaves has an Mr of 400000. The native enzyme molecule is a homotetramer. The amino acid composition of PEPC is determined. The enzyme contains 8 half-cystine residues per subunit. The role of half-cystine residues and the steric arrangement of the enzyme protein molecule are discussed

Residential Building - Lesná

Stavba bytového domu se nachází v městské čtvrti Lesná, na ulici Dřínová. Budova tvoří přechod mezi dvoupodlažními řadovými domy a šestipodlažními terasovými bytovými domy umístěnými výš na terénu. Tvar stavby je definován zejména postavením okolních budov a sklonitým terénem, na kterém je budova umístěna. Je rozdělena příčně na dva bloky, mezi kterými vzniká prostor pro odpočinek a relaxaci. Tyto bloky jsou pak mezi sebou spojeny betonovými mostky. Zadáním bylo koncipovat budovu jako luxusní bytový dům s velice prostornými byty, proto lze na této stavbě pozorovat nejen tyto prostorově velkorysé plochy, ale jsou zde znát i technické a materiálové možnosti dnešní doby. Například ve formě velkoplošných oken, tmavých, hliníkových, fasádních panelů ALUCOBOND nebo vjezdu do garáží prostřednictvím auto-výtahu.The block of flats is located at the Lesná distrikt, on the Dřínová street. This building forms transition between two-storey row houses and six story terraced houses, which are situated up on the terrain. Form of the building is defined especially by positions of surrounding houses and by the hill, which is placed on. Building is dividend transversely to two blocks, which are connected by concrete bridges. Between these blocks is a space for repose and relaxation. The task was to design the building as a luxury apartment building with very spacious flats, therefore it is possible to observe not only the these generous areas, but there are technical and material possibilities of these times too. For example large windows, dark, aluminum, facade, profiles ALUCOBOND or entrance to the garage via car-lift.