A POSSIBLE ROLE FOR PROTEIN-KINASE-C IN CO2 H+-INDUCED C-FOS MESSENGER-RNA EXPRESSION IN PC12 CELLS/

Recently we have found that hypercapnia induces nuclear protein (FOS) expression in the brainstem chemosensitive neurons, including catechol amine-containing cells. In the present studies we examined the role of protein kinase C (PKC) pathway in CO2-induced c-fos expression. Becau se of the complexity of the CNS system, experiments were performed in pheochromocytoma cells (PC12 cells). These cells originate from neuron al crest and express catecholaminergic traits. We depleted PKC from PC 12 cells by prolonged (48 h) exposure to high concentration of phorbol 12-myristate, 13-acetate (PMA, 100 nM), and then determined the expre ssion of: (I) c-fos mRNA by Northern blot (2) PKC isoforms, tyrosine p hosphorylated and unphosphorylated MAP (mitogen activated protein) kin ases by Western blot. Depletion of PKC abolished the effect of CO2 on c-fos mRNA expression, inhibited MAP kinases tyrosine phosphorylation and suppressed the expression of PKCalpha and PKCzeta. These results s uggest that MAP kinases, PKCalpha and/or PKCbeta might be involved in CO2-induced c-fos mRNA expression. (C) 1998 Elsevier Science B.V. All rights reserved.