A specific inhibitor of protein kinase C induces differentiation of neuroblastoma cells.
Recent reports suggest that protein kinase C is involved in neural differentiation. We show that 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H7), the more specific inhibitor of protein kinase C known, induces morphological and functional differentiation of neuro 2a cells, as indicated by the marked increase in the number of neurites/cell and in acetylcholinesterase activity. HA 1004 does not induce differentiation of neural cells. The induction of differentiation by H7 was very rapid; 3 h after addition of H7 the percentages of differentiated cells were 17, 33, 37, 55, and 75% for 17, 50, 85, 250, and 500 microM H7, respectively, while for controls it was 9%. When 500 microM H7 was added to the culture medium, protein kinase C was inhibited by 72 and 62% in cytosol and membrane, respectively. Also, acetylcholinesterase activity (a marker of functional differentiation) increased with time, reaching a 7-fold increase after 48 h.
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Instituto de Investigaciones Citológicas de la Caja de Ahorros de Valencia, Centro Asociado del Consejo Superior de Investigaciones Científicas, Spain.
Miñana
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Grisolía
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D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002462:Cell Membrane / Q000201:enzymology; D003600:Cytosol / Q000201:enzymology; D007546:Isoquinolines / Q000494:pharmacology*; D007700:Kinetics; D051379:Mice; D009447:Neuroblastoma; D010879:Piperazines / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D013449:Sulfonamides; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology
D002121:Calcium Channel Blockers; D007546:Isoquinolines; D010879:Piperazines; D013449:Sulfonamides; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C043204:N-(2-guanidinoethyl)-5-isoquinolinesulfonamide; D011493:Protein Kinase C