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

Yan, Lizhen, Volker Herrmann, Jason K. Hofer, and Paul A. Insel. b-Adrenergic receptor/cAMP-mediated signaling and apoptosis of S49 lymphoma cells. Am J Physiol Cell Physiol 279: C1665–C1674, 2000.—b-Adrenergic receptor (bAR) 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 bARmediated 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., bAR 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 Gsa and functional protein kinase A (PKA), respectively, bAR activation of Gsa 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 bAR activation induces apoptosis in immature T lymphocytes via Gsa and PKA, while overexpression of Bcl-2 prevents cell death. bAR/cAMP/PKA-mediated apoptosis may provide a means to control proliferation of immature T cells in vivo.