Wynik wyszukiwania w bazie Polska Bibliografia Lekarska GBL

Zapytanie: SAFIEH-GARABEDIAN
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Tytuł oryginału: Inhibiton of glutathione-related enzymes augments LPS-mediated cytokine biosynthesis: involvement of an IkB/NF-kB-sensitive pathway in the alveolar epithelium.
Autorzy: Haddad John J., Safieh-Garabedian Bared, Saad‚ Nayef E., Lauterbach Ryszard
Źródło: Int. Immunopharmacol. 2002: 2 (11) s.1567-1583, il., tab., bibliogr. 45 poz.
Sygnatura GBL: 313,577

Hasła klasyfikacyjne GBL:
  • pulmonologia

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

    Wskaźnik treści:
  • zwierzęta
  • szczury

    Streszczenie angielskie: The regulation of lipopolysaccharide (LPS)-mediated pro-inflammatory cytokine biosynthesis by reduction by reduction-oxidation (redox)-sensitive enzymes involved in maintaining intracellular glutathione homeostasis was onvestigated in fetal alveolar type II epithelial cells (fATII). Inhibition of glutathione-oxidized disulfide reductase, which recycles GSSG - 2GSH, by the action of 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) augmented LPS-depenfent secretion of interleukin (IL)-1á, IL-6 and tumor necrosis factor (TNF)-ŕ. BCNU incresed [GSSG] concentration at the expense of [GSH], thereby favoring oxidation equilibrium. Inhibition of ç-glutamylcysteine synthetase, the rate-limiting enzyme in the biosynthesis of GSH, by the action of L=buthionine-(S,R)-sulfoxime (BSO), potentiated LPS-induced IL-1á, IL-6 and TNF-ŕ production. Similar to BCNU, BSO depleted [GSH] and induced the accumulation of [GSSG]. BCNU and BSO reduced LPS-mediated phosphorylation of inhibitory-kB (IkB-ŕ), allowing its cytosolic accumulation. This effect was associated with the inhibition of the nuclear translocation of selective nuclear factor (NF)-kB subunits: NF-kB1 (p50), RelA (p65), RelB (p68) and c-Rel 9p75), but not NFkb2 (p52). BCNU and BSO reduced LPS-induced NF-kB activation as determined by the electrophoretic mobility shift DNA-binding assay. Analytical analysis of the effect of modulating the dynamic redox ratio [GSH]+[GSSG])[GSSG] revealed a novel role for GSSG as a disulfhydryl compound which an inhibitory effect on NF-kB activation. In is concluded that selective modulation...

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