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

Abstract

β-Adrenergic receptor (βAR) activation and/or increases in cAMP regulate growth and proliferation of a variety of cells and, in some cells, promote cell death. In the current studies we addressed the mechanism of this growth reduction by examining βAR-mediated effects in the murine T-lymphoma 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., βAR agonists, 8-bromo-cAMP, cholera toxin, forskolin). Morphological and biochemical criteria indicate that this cell death is a result of apoptosis. In cyc−and kin−S49 cells, which lack Gsα and functional protein kinase A (PKA), respectively, βAR activation of Gsα and cAMP action via PKA are critical steps in this apoptotic pathway. S49 cells that overexpress Bcl-2 are resistant to cAMP-induced apoptosis. We conclude that βAR activation induces apoptosis in immature T lymphocytes via Gsα and PKA, while overexpression of Bcl-2 prevents cell death. βAR/cAMP/PKA-mediated apoptosis may provide a means to control proliferation of immature T cells in vivo.