EXTRACELLULAR H-FOS( STIMULATES THE EXPRESSION OF C)C-JUN MESSENGER-RNA THROUGH CA2+/CALMODULIN IN PC12 CELLS/

Evidence has accumulated that an increase in extracellular protons sti mulates the transmembrane mechanism to induce various intracellular re sponses, such as the expression of c-Jos and c-jun. In the present stu dy, we aimed to obtain evidence that an increase in extracellular prot ons induces expression of c-fos/c-jun mRNA in PC12 pheochromocytoma ce lls of rats. We found that the c-fos/c-jun mRNA expression increased w hen extracellular pH was decreased gradually from 7.40 to 7.20 and tha t there was a significant correlation between extracellular pH values and the expression of c-fos/c-jun mRNA. To determine whether the Ca2+/ calmodulin system subserves the Ht-induced expression of c-fos/c-jun, Ca2+/calmodulin inhibitor trifluoperazine was added to PC12 cells. We found that trifluoperazine inhibited the expression of the H(+)induced c-fos/c-jun mRNA by 30-35%. In contrast, trifluoperazine did not inhi bit the expression of phorbol-induced c-fos/c-jun mRNA. These results indicate that an increase in extracellular protons induces the express ion of c-fos/c-jun mRNA, and this expression is mediated partly by the Ca2+/calmodulin system. CELL SIGNAL 10;7:499-503, 1998. (C) 1998 Else vier Science Inc.