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Cardiovascular Research 1997 33(3):631-640; doi:10.1016/S0008-6363(97)00005-9
© 1997 by European Society of Cardiology
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Copyright © 1997, European Society of Cardiology

cAMP-mediated c-fos expression in pressure-overloaded acceleration of protein synthesis in adult rat heart

Junzo Osaki*, Takashi Haneda, Hirotsuka Sakai and Kenjiro Kikuchi

First Department of Internal Medicine, Asahikawa Medical College, Nishikagura 4-5, Asahikawa, Hokkaido 078, Japan

Objectives: The aim was to determine whether proto-oncogene c-fos expression and acceleration of protein synthesis by acute pressure overload to the heart were coupled with a cAMP- and protein-kinase-A-dependent system in adult rat heart. Methods: Isolated adult rat hearts were perfused as Langendorff preparations at a constant aortic pressure of 60 mmHg. In the pressure-overloaded group, aortic pressure was raised from 60 to 120 mmHg for the time indicated. Agents that increase cAMP were added to the perfusate at an aortic pressure of 60 mmHg. Furthermore, a selective protein kinase A inhibitor (H-89) or a selective protein kinase C inhibitor (calphostin C) was administered before the elevation of aortic pressure or the addition of the agents. cAMP content or rates of protein synthesis were measured by RIA or the incorporation of [14C]phenylalanine into total heart protein, respectively, -fos mRNA expression was determined by Northern blot analysis. Results: Elevation of aortic pressure in beating hearts and arrested hearts increased cAMP content at 2 min of perfusion by 36 and 41%, induced c-fos mRNA expression at 30–60 min of perfusion by 4.8- and 2.0-fold, and accelerated rates of protein synthesis during the 2nd hour of perfusion by 39 and 41% over control levels, respectively. Glucagon, forskolin or IBMX mimicked increases in these parameters by elevated aortic pressure. H-89 prevented these changes by elevated pressure overload or exposure to forskolin or IBMX in arrested hearts. On the other hand, calphostin C prevented the pressure-induced increases in c-fos expression and protein synthesis rates in arrested hearts. Conclusions: These results suggest that c-fos expression induced by acute pressure overload may be coupled with increased cAMP content and protein kinase A activity in addition to increased protein kinase C activity in adult rat heart.

KEYWORDS c-fos; c-AMP; Protein kinase A; Protein kinase C; Pressure overload; Protein synthesis; Hypertrophy; Rat, heart


* Corresponding author. Tel. +81 166 652111, ext. 2442; Fax +81 166 659473.


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