A possible role for protein kinase C in CO2/H+-induced c-fos mRNA expression in PC12 cells

Recently we have found that hypercapnia induces nuclear protein (FOS) expression in the brainstem chemosensitive neurons, including catecholamine-containing cells. In the present studies we examined the role of protein kinase C (PKC) pathway in CO₂-induced c-fos expression. Because of the complexity of the CNS system, experiments were performed in pheochromocytoma cells (PC12 cells). These cells originate from neuronal crest and express catecholaminergic traits. We depleted PKC from PC12 cells by prolonged (48 h) exposure to high concentration of phorbol 12-myristate, 13-acetate (PMA, 100 nM), and then determined the expression of: (1) c-fos mRNA by Northern blot (2) PKC isoforms, tyrosine phosphorylated and unphosphorylated MAP (mitogen activated protein) kinases 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 PKC_α and PKC_ζ. These results suggest that MAP kinases, PKC_α and/or PKC_β might be involved in CO₂-induced c-fos mRNA expression.