Selective activation of protein kinase C isoforms by angiotensin II in neuroblastoma X glioma cells

Differential activation of PKC isoforms by angiotensin II (AII) has been found in a variety of tissues in which this important octapeptide mediates its multitude of effects. To date, the PKC isoforms involved in mediating brain-specific effects are yet to be defined. In the present study, the identity of PKC isoforms coupled to All stimulation was examined in the neuroblastom X glioma hybrid cell line, NG108-15, by Western blot analysis. This cell line expresses both the AT1 and AT2 receptor subtypes, with the AT1 subtype predominating, and expression levels highly-upregulated when cells are in the differentiated state. Six PKC isoforms were examined in the present study, including three Ca2+ dependent (alpha, beta, and gamma), and three Ca2+ independent (delta, epsilon, and zeta) isoforms. NG108-15 cells were found to express PKC alpha, delta, epsilon and zeta isoforms but not beta or gamma isoforms. Differential sensitivity of the PKC isoforms to All stimulation was demonstrated, with All causing a rapid and transient activation of the PKC alpha only in undifferentiated cells, whereas both PKC alpha and epsilon isoforms were responsive in differentiated cells. PKC activation was found to be both dose- and time-dependent. The data demonstrate the differential activation of PKC isoforms to All stimulation in NG108-15 cells, with evidence suporting the involvement of the PKC alpha and epsilon isoforms in All-mediated effects in the brain. (C) 2003 Elsevier Ireland Ltd. All rights reserved.