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 AII stimulation was examined in the neuroblastoma 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 Ca(2+) dependent (alpha, beta, and gamma), and three Ca(2+) independent (delta, and zeta) isoforms. NG108-15 cells were found to express PKC alpha, delta, and zeta isoforms but not beta or gamma isoforms. Differential sensitivity of the PKC isoforms to AII stimulation was demonstrated, with AII causing a rapid and transient activation of the PKC alpha only in undifferentiated cells, whereas both PKC alpha and 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 AII stimulation in NG108-15 cells, with evidence supporting the involvement of the PKC alpha and isoforms in AII-mediated effects in the brain.
Greenland
Karen J
KJ
Institute for Hormone and Fertility Research, University of Hamburg, Grandweg 64, Hamburg 22529, Germany. karen.greenland@mcri.edu.au
Mukhopadhyay
Amal K
AK
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001923:Brain Chemistry; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004789:Enzyme Activation; D006822:Hybrid Cells; D051379:Mice; D009447:Neuroblastoma / Q000201:enzymology* / Q000378:metabolism; D009474:Neurons / Q000201:enzymology / Q000378:metabolism; D020033:Protein Isoforms / Q000032:analysis / Q000378:metabolism; D011493:Protein Kinase C / Q000032:analysis / Q000378:metabolism*; D051571:Protein Kinase C-alpha; D021381:Protein Transport; D051381:Rats; D011945:Receptors, Angiotensin / Q000378:metabolism
D020033:Protein Isoforms; D011945:Receptors, Angiotensin; D000804:Angiotensin II; C496630:Prkca protein, mouse; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha