Barium modulates c-fos expression and post-translational modification

The addition of exogenous barium ions to PC12 rat pheochromocytoma cells elicits a transient induction of the c-fos gene. Induction is antagonized by extracellular calcium and the dihydropyridine calcium channel blockers, and it is attenuated in the presence of calmodulin inhibitors. Thus, barium appears to enter the cell through a voltage-dependent calcium channel and, either directly or indirectly, interacts with calmodulin to stimulate c-fos expression. This property of barium is not shared by a range of di- and trivalent cations examined. Agents that induce the c-fos gene in PC12 cells may be divided into two broad categories. The first comprises polypeptide growth factors and phorbol esters, which give rise to a c-fos protein that undergoes extensive post-translational modification. The second, which comprises depolarizing agents and barium ions, acts via calcium channels and yields a c-fos protein that undergoes less extensive post-translational modification. These different forms of c-fos protein can be distinguished on the basis of their apparent molecular weights on sodium dodecyl sulfate/polyacrylamide gels.