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.