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Expression of p53 during apoptosis induced by D-galactosamine and the protective role of PGE1 in cultured rat hepatocytes.

Abstract

p53 is a critical player in the prevention of tumor development. It can contribute directly to DNA repair and inhibition of angiogenesis and subsequently to the induction of apoptosis. The regulation of p53 expression is mediated by the transcription factor NF-kappaB. This includes regulation of p53 protein stability, control of its subcellular localization and conformational changes that allow activation of the DNA binding activity of p53. Rat hepatocytes were isolated from male Wistar rats following collagenase perfusion of liver. We examined the change in the expression level of p53 by western blotting in hepatocytes and its effect on apoptosis as a response of treatment with D-galactosamine, prostaglandin E1 and/or the Proteosome Inhibitor (PSI). A kinetic study of the extracellular lactate dehydrogenase activity, NF-kappaB activation, induced nitric oxide synthase expression and nitric oxide production was carried out in hepatocytes. The addition of prostaglandin E1 to control and D-galactosamine-treated hepatocytes increased p53 expression in the cytoplasm during 24 h. While the addition of PSI in the absence of prostaglandin E1 decreased p53 expression at 5 mM D-galactosamine. This inhibition is reversed in the presence of prostaglandin E1 at 5 and 40 mM D-galactosamine. The protective action of prostaglandin E1 against the apoptotic effect of D-galactosamine is mediated by NF-kappaB activation, induced nitric oxide synthase and p53 expression.

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  • Aggregator Full Text
  • Authors

    Fouad D, Ataya FS, Muntane J

    Source

    Pakistan journal of biological sciences: PJBS 14:21 2011 Nov 1 pg 976-83

    MeSH

    Alprostadil
    Animals
    Apoptosis
    Cell Death
    Cells, Cultured
    Cytoplasm
    Galactosamine
    Hepatocytes
    L-Lactate Dehydrogenase
    Male
    NF-kappa B
    Necrosis
    Nitric Oxide
    Nitric Oxide Synthase
    Proteome
    Rats
    Rats, Wistar
    Tumor Suppressor Protein p53

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    22514887