beta-Adrenergic receptor/cAMP-mediated signaling and apoptosis of S49 lymphoma cells

beta-Adrenergic receptor (beta AR) activation and/or increases in cAMP regu late growth and proliferation of a variety of cells and, in some cells, pro mote cell death. In the current studies we addressed the mechanism of this growth reduction by examining beta AR-mediated effects in the murine T-lymp homa cell line S49. Wild-type S49 cells, derived from immature thymocytes ( CD4(+)/CD8(+)) undergo growth arrest and subsequent death when treated with agents that increase cAMP levels (e.g., beta AR agonists, 8-bromo-cAMP, ch olera toxin, forskolin). Morphological and biochemical criteria indicate th at this cell death is a result of apoptosis. In cyc(-) and kin(-) S49 cells , which lack G(s)alpha and functional protein kinase A (PKA), respectively, beta AR activation of Gs a and cAMP action via PKA are critical steps in t his apoptotic pathway. S49 cells that overexpress Bcl-2 are resistant to cA MP-induced apoptosis. We conclude that beta AR activation induces apoptosis in immature T lymphocytes via G(s)alpha and PKA, while overexpression of B cl-2 prevents cell death. beta AR/cAMP/PKA-mediated apoptosis may provide a means to control proliferation of immature T cells in vivo.