Cyclic mechanical strain causes cAMP-response element binding protein activation by different pathways in cardiac fibroblasts
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....
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2010-02-01
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doaj-9924ae448f294198987193cc0a9d21df2020-11-24T21:15:34ZengTouch Medical MediaHeart International1826-18682036-25792010-02-0151e3e310.4081/hi.2010.e3Cyclic mechanical strain causes cAMP-response element binding protein activation by different pathways in cardiac fibroblastsBritta HusseGerrit IsenbergThe 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.http://www.pagepress.org/journals/index.php/hi/article/view/1032Heart, Cardiac fibroblasts, Mechanical strain, Signal transduction, |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Britta Husse Gerrit Isenberg |
spellingShingle |
Britta Husse Gerrit Isenberg Cyclic mechanical strain causes cAMP-response element binding protein activation by different pathways in cardiac fibroblasts Heart International Heart, Cardiac fibroblasts, Mechanical strain, Signal transduction, |
author_facet |
Britta Husse Gerrit Isenberg |
author_sort |
Britta Husse |
title |
Cyclic mechanical strain causes cAMP-response element binding protein activation by different pathways in cardiac fibroblasts |
title_short |
Cyclic mechanical strain causes cAMP-response element binding protein activation by different pathways in cardiac fibroblasts |
title_full |
Cyclic mechanical strain causes cAMP-response element binding protein activation by different pathways in cardiac fibroblasts |
title_fullStr |
Cyclic mechanical strain causes cAMP-response element binding protein activation by different pathways in cardiac fibroblasts |
title_full_unstemmed |
Cyclic mechanical strain causes cAMP-response element binding protein activation by different pathways in cardiac fibroblasts |
title_sort |
cyclic mechanical strain causes camp-response element binding protein activation by different pathways in cardiac fibroblasts |
publisher |
Touch Medical Media |
series |
Heart International |
issn |
1826-1868 2036-2579 |
publishDate |
2010-02-01 |
description |
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. |
topic |
Heart, Cardiac fibroblasts, Mechanical strain, Signal transduction, |
url |
http://www.pagepress.org/journals/index.php/hi/article/view/1032 |
work_keys_str_mv |
AT brittahusse cyclicmechanicalstraincausescampresponseelementbindingproteinactivationbydifferentpathwaysincardiacfibroblasts AT gerritisenberg cyclicmechanicalstraincausescampresponseelementbindingproteinactivationbydifferentpathwaysincardiacfibroblasts |
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