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J. Biol. Chem., Vol. 265, Issue 17, 9599-9601, Jun, 1990

A specific inhibitor of protein kinase C induces differentiation of neuroblastoma cells

V Felipo, MD Minana and S Grisolia
Instituto de Investigaciones Citologicas de la Caja de Ahorros de Valencia, Centro Asociado del Consejo Superior de Investigaciones Cientificas, Spain.

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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J. Biol. Chem.Home page
F. Ronca, S.-L. Chan, and V. C. Yu
1-(5-Isoquinolinesulfonyl)-2-methylpiperazine Induces Apoptosis in Human Neuroblastoma Cells, SH-SY5Y, through a p53-dependent Pathway
J. Biol. Chem., February 14, 1997; 272(7): 4252 - 4260.
[Abstract] [Full Text] [PDF]


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J. Cell Sci.Home page
M. J. Clemens, I. Trayner, and J. Menaya
The role of protein kinase C isoenzymes in the regulation of cell proliferation and differentiation
J. Cell Sci., December 1, 1992; 103(4): 881 - 887.
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