Wynik wyszukiwania w bazie Polska Bibliografia Lekarska GBL

Zapytanie: DARZYNKIEWICZ
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Tytuł oryginału: The modulation of the DNA-damaging effect of polycyclic aromatic agents by xanthines. P. 1: Reduction of cytostatic effects of quinacrine mustard by caffeine.
Autorzy: Kapuściński Jan, Ardelt Barbara, Piosik Jacek, Zdunek Małgorzata, Darzynkiewicz Zbigniew
Źródło: Biochem. Pharmacol. 2002: 63 (4) s.625-634, il., tab., bibliogr. 45 poz.
Sygnatura GBL: 304,395

Hasła klasyfikacyjne GBL:
  • genetyka
  • farmacja

    Typ dokumentu:
  • praca kliniczna
  • praca opublikowana za granicą
  • tytuł obcojęzyczny

    Wskaźnik treści:
  • ludzie

    Streszczenie angielskie: Recently, accumulated statistical data indicate the protective effect of caffeine consumption against several types of cancer diseases. There are also reports about protective effect of caffeine and other xanthines against tumors induced by polycyclic aromatic hydrocarbons. One of the explanations is based on biological activation of such carcinogens by cytochromes that are also known for metabolism of caffeine. However, there is also numerous data indicating reverse effect on cytotoxicity of anticancer drugs that inhibit the action of topoisomerase I (e.g. Camptothecin or Topotecan) and topoisomerase II inhibitors (e.g. Doxorubicin, Mitoxantrone or mAMSA). In this work we tested the hypothesis that the caffeine protective effect is the result of sequestering of aromatic mutagens by formation of stacking (ă - ă) complex. As the models for the study we have chosen two well-known mutagens, that do not require metabolic activation: quinacrine mustard (QM, aromatic, heterocyclic nitrogen mustard) and mechlorethamine (NM2, aliphatic nitrogen mustard). The flow cytometry study of these agents' action on the cell cycle of HL-60 cells indicated that caffeine prevents the cytotoxic action of QM, but not that of NM2. The formations of stacking complexes of QM with caffeine were confirmed by light absorption, calorimetric measurements and by molecular modeling calculation. Using the statistical thermodynamics calculations we calculated the "neighborhood" association constant (KAC = 59 ń 2 M**-1) and enthalpy change (DeltaH**0' = -116 cal mol**-1); the favorable entropy change of complex formation (DeltaS**0' = 7.72 cal mol**-1 K**-1, ...

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    Tytuł oryginału: In situ activation of caspases and serine proteases during apoptosis detected by affinity labeling their enzyme active centers with fluorochrome-tagged inhibitors.
    Autorzy: Grabarek Jerzy, Darzynkiewicz Zbigniew
    Źródło: Exp. Hematol. 2002: 30 (9) s.982-989, il., bibliogr. 60 poz.
    Sygnatura GBL: 305,749

    Typ dokumentu:
  • praca opublikowana za granicą
  • tytuł obcojęzyczny

    Streszczenie angielskie: Activation of caspases is the key event of apoptosis. To detect this event in situ we applied fluorochrome-labeled inhibitors of caspases (FLICA) as affinity of activity centers of these enzymes. The FLICA are fluoroscein- or sulforhodamine-conjugated peptide-fluoromethyl ketones that covalently, with 1:1 stoichiometry, bind to enzymatic centers of caspases; the specifity is provided by the peptide sequence of amino acids. Similarly, we applied fluorescent inhibitors of serine proteases (FLISP) to detected activite sites of the latter enzymes. Exposure of live cells to FLICA of FLISP led to uptake of these ligands and their binding to activated caspases or active sites og serine proteases; the unbound reagents were removed by cell rinse. Only cells undergoing apoptosis were labeled with FLISP or FLICA. Intracellular binding sites of FLICA are consistent with known localization of caspases. Covalent binding of FLICA or FLIPPS allowed us to identify the labeled proteins by immunoblotting: the proteins that bound individual FLICAs had molecular weight between 17 and 22 kDa, which corresponds to large subunits of the caspases; two proteins reacting with FLISP were about 57 and 60 kDa, which suggests that they are novel enzymes. Detection of caspases or serine proteases activation can be combined with other markers of apoptosis or cell cycle for multiparametric analysis by flow or laser ascanning cytometry. Being caspases inhibitors, FLICA arrest the process of apoptosis and prevent cell distintegration. The stathmo-apoptotic assay was developed...

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