title: 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.
authors.affiliation: Department of Zoology, College of Science, Center for Scientific and Medical Female Colleges, King Sand University, P.O. Box 22452-11459, Riyadh, Saudi Arabia.
authors.forename: D
authors.initials: D
authors.lastname: Fouad
authors.forename: F S
authors.initials: FS
authors.lastname: Ataya
authors.forename: J
authors.initials: J
authors.lastname: Muntane
mesh_terms: D000527:Alprostadil / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D005688:Galactosamine / Q000494:pharmacology*; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009336:Necrosis; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D020543:Proteome / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D016328:NF-kappa B; D020543:Proteome; D016159:Tumor Suppressor Protein p53; D009569:Nitric Oxide; D005688:Galactosamine; D007770:L-Lactate Dehydrogenase; D019001:Nitric Oxide Synthase; D000527:Alprostadil