Effects of beta-adrenoceptors overexpression on cell survival are mediated by Bax/Bcl-2 pathway in rat cardiac myocytes

Background: Chronic activation of beta-adrenoceptors (beta-ARs) results in cardiac myocyte injury, even death, and diminishes the number of beta-ARs. Objectives: To investigate the effects of overexpression of beta(1)- or beta(2)-AR on cardiomyocytes injured by isoprenaline (ISO). Methods: We have used an adenoviral vector carrying the sequence for human beta(1)- or beta(2)-AR (Adv.beta(1), Adv.beta(2)) to increase the content of beta, or beta(2)-AR in isolated adult rat ventricular myocytes, and we have examined the cell survival and the expression of Bax and Bcl-2. Results: With use of adenoviral vectors, the beta(1)- and beta(2)-AR contents of myocytes were increased 2.98- and 2.87-fold, respectively. Overexpression of beta(1)-AR sharpened the cellular injury of ISO. If beta(2)-AR activity was further blocked by addition of selective beta(2)-AR antagonist ICI118,551, the cells were more sensitive to the impairment of Adv.beta(1) + ISO. Overexpression of Adv.beta(2) partially inversed the cytotoxicity of ISO stimulation. The beneficial effects were strengthened by addition of CGP20712A, a beta(1)-AR-blocking agent. Western blot analysis demonstrated that both increasing beta(1)-AR and inhibition of beta(2)-AR increased the ratio of Bax/Bcl-2. Whereas, increasing beta(2)-AIR and inhibition of beta(1)-AR decreased the ratio of Bax/Bcl-2. Control adenovirus CGP had no effect on cell survival. Conclusions: Overexpression of Adv.beta(2) and/or inhibition of beta(1)-AR have protective effect on adult rat ventricular myocytes chronically stimulated by ISO. Overexpression of Adv.beta(1) and/or inhibition Of beta(2)-AR are deleterious in the same state. The effects of beta-ARs on cell survival might be mediated by the Bax/Bcl-2 signal pathway. Copyright (c) 2006 S. Karger AG, Basel.