%0 Journal Article
%T Cyclic mechanical strain causes cAMP-response element binding protein activation by different pathways in cardiac fibroblasts
%A Britta Husse
%A Gerrit Isenberg
%J Heart International
%D 2010
%I Wichtig Editore, Milan
%R 10.4081/hi.2010.e3
%X The transcription factor cAMP-response element binding protein (CREB) mediates the mechanical strain-induced gene expression in the heart. This study investigated which signaling pathways are involved in the strain-induced CREB activation using cultured ventricular fibroblasts from adult rat hearts. CREB phosphorylation was analyzed by immunocytochemistry and ELISA. Cyclic mechanical strain (1 Hz and 5% elongation) for 15 min induced CREB phosphorylation in all CREB-positive fibroblasts. Several signaling transduction pathways can contribute to strain-induced CREB activation. The inhibition of PKA, PKC, MEK, p38-MAPK or PI3-kinase partially reduced the strain-induced CREB phosphorylation. Activation of PKA by forskolin or PKC by PMA resulted in a level of CREB phosphorylation comparable to the reduced level of the strain-induced CREB phosphorylation in the presence of PKA or PKC inhibitors. Signaling pathways involving PKC, MEK, p38-MAPK or PI3-kinase seem to converge during strain-induced CREB activation. PKA interacted additively with the investigated signaling pathways. The strain-induced c-Fos expression can be reduced by PKC inhibition but not by PKA inhibition. Our results suggest that the complete strain-induced CREB phosphorylation involves several signaling pathways that have a synergistic effect. The influence on gene expression is dependent on the level and the time of CREB stimulation. These wide-ranging possibilities of CREB activation provide a graduated control system.
%K Heart
%K Cardiac fibroblasts
%K Mechanical strain
%K Signal transduction
%U http://www.pagepress.org/journals/index.php/hi/article/view/1032