title: The selective protein kinase C inhibitor GF 109203X inhibits phorbol ester-induced morphological and functional differentiation of SH-SY5Y human neuroblastoma cells.
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.
authors.affiliation: Department of Biochemistry and Pharmacy, Abo Akademi University, BioCity, Turku, Finland.
authors.forename: J
authors.initials: J
authors.lastname: Heikkilä
authors.forename: A
authors.initials: A
authors.lastname: Jalava
authors.forename: K
authors.initials: K
authors.lastname: Eriksson
mesh_terms: D015152:Blotting, Northern; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D019922:GAP-43 Protein; D015870:Gene Expression / Q000187:drug effects; D016762:Genes, fos / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D007700:Kinetics; D008301:Maleimides / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D008970:Molecular Weight; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D016501:Neurites / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D009447:Neuroblastoma; D009478:Neuropeptide Y / Q000096:biosynthesis; D010750:Phosphoproteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D000090063:Proto-Oncogene Mas; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis / Q000187:drug effects / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D019922:GAP-43 Protein; D007211:Indoles; C000715470:MAS1 protein, human; D008301:Maleimides; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D009478:Neuropeptide Y; D010750:Phosphoproteins; D000090063:Proto-Oncogene Mas; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D011493:Protein Kinase C; C070515:bisindolylmaleimide I; D013755:Tetradecanoylphorbol Acetate