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  • Title: Inhibition by modified oligodeoxynucleotides of the expression of type-1 plasminogen activator inhibitor in human endothelial cells.
    Author: Cierniewski CS, Babinska A, Swiatkowska M, Wilczynska M, Okruszek A, Stec WJ.
    Journal: Eur J Biochem; 1995 Jan 15; 227(1-2):494-9. PubMed ID: 7851428.
    Abstract:
    Antisense phosphodiester and phosphorothioate oligodeoxynucleotides (23-residue or 24-residue oligodeoxynucleotides) were constructed for sequences of type-1 plasminogen-activator-inhibitor mRNA to assess their capability to modulate type-1 plasminogen-activator-inhibitor-mediated fibrinolysis. Antisense oligodeoxynucleotides were targeted at the mRNA sequence coding a signal peptide, at a part of the reactive center Ile342-Pro349, and at an internally translated segment Asn265-Leu272. The effect of antisense oligonucleotides on the concentration of type-1 plasminogen activator inhibitor in conditioned media and human endothelial cells was determined by the activity test with fibrin as a substrate, and by immunoprecipitation after metabolic labelling of cells with [35S]methionine. Three phosphorothioate oligodeoxynucleotides were specifically inhibitory while phosphodiester oligodeoxynucleotides with the same sequence did not show any activity. Phosphorothioate oligodeoxynucleotides 2, 4 and 6 inhibited the synthesis of type-1 plasminogen activator inhibitor in endothelial cells in a time-dependent and concentration-dependent manner. These data suggest that antisense oligodeoxynucleotides may be useful in the design of antithrombolytic therapeutics.
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