AbstractBackround and Aims
It has been shown that transmembrane, G-protein-coupled adenylylcyclases play an important role in β-adrenergic stimulation-induced cardiac hypertrophy. However, the role of cytosolically localized type 10 "soluble" adenylylcyclase (sAC) in hypertrophy development is unknown. Previous reports demonstrated that sAC is located in nuclei and controls activity of the cAMP response element binding (CREB), a transcription factor significantly contributing in the development of hypertrophy. In the present study we aimed to prove the role of sAC in cardiac hypertrophy.Methods and Results
For this purpose adult rat ventricular cardiomyocytes were treated with 10 μM isoproterenol (ISO) and 1 μM ICI 118,551 hydrochloride, a β2-adrenoceptor antagonist, for 24 h. The development of hypertrophy was evaluated by cell size, protein content and expression of α-skeletal actin.Methods and Results
As expected, β1-adrenergic stimulation led to an enhancement in all these parameters. Simultaneous treatment with specific sAC inhibitor KH7 (12,5 μM) prevented these effects, whereas KH7 did not affect control cells significantly. Only at concentrations higher than 12,5 μM toxic effects were observed. Therefore, sh-RNA for specific sAC knockdown was generated. sAC knockdown (adenoviral shRNA-transfection), which was evaluated by western blotting, attenuated the development of hypertrophy under β1-adrenergic stimulation.Methods and Results
Altogether, results of this study suggest a potential role of sAC in β1-adrenergic stimulation-induced hypertrophy of adult cardiomyocytes.