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  • Title: The selective protein kinase C inhibitor GF 109203X inhibits phorbol ester-induced morphological and functional differentiation of SH-SY5Y human neuroblastoma cells.
    Author: Heikkilä J, Jalava A, Eriksson K.
    Journal: Biochem Biophys Res Commun; 1993 Dec 30; 197(3):1185-93. PubMed ID: 8280132.
    Abstract:
    Previous attempts to inhibit the phorbol ester 12-O-tetradecanoyl phorbol 13-acetate (TPA) -induced differentiation of SH-SY5Y neuroblastoma cells by non-specific inhibitors of protein kinases have failed. In the present study we have used the bisindolylmaleimide GF 109203X, which is a potent and selective inhibitor of protein kinase C (PKC). GF 109203X effectively antagonized TPA-stimulated phosphorylation of an endogenous 80 kDa PKC substrate. The compound blocked neurite outgrowth and rounding up of cells induced by the phorbol ester. In addition, GF 109203X completely inhibited TPA-induced increase in cellular content of noradrenaline as well as stimulation of expression of neuropeptide Y, growth-associated protein-43 and c-fos proto-oncogene mRNA by TPA. The inhibition of the TPA-induced effects by GF 109203X was dose-dependent.
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