Catecholamine mediated S49 T lymphoma apoptosis is regulated by p38 MAPK (136.15)

Abstract

Abstract p38 MAPK is an important intracellular signaling mediator for a variety of cellular and environmental stressors and plays a role in cell survival, apoptosis, and inflammation. Previously, our lab has shown that norepinephrine (NE) treatment of S49 T lymphoma cells leads to increased activity of p38 MAPK by the classical βAR/AC/cAMP/PKA pathway. Exogenous cAMP or βAR stimulation of S49 cells leads to apoptosis. To study the relationship between p38 MAPK activity and apoptosis, S49 cells were incubated in the presence and absence of a cAMP analogue (8-bromo) with or without the p38 MAPK inhibitor SB203580. After 72 hours of cAMP treatment, S49 cell viability decreased by 50%, yet in the presence of SB203580 cell viability decreased by 35%. The steady state levels of FasL mRNA (an early biochemical marker of apoptosis) were analyzed after two hours of S49 cell treatment with 8-bromo cAMP in the absence or presence of SB203580. FasL mRNA levels increased 9.8 fold with 8-bromo cAMP treatment for 2 hours and was reversed 50% by p38 MAPK inhibition. These results suggest that activation of p38 MAPK by NE or cAMP is associated with T lymphoma cell apoptosis. Supported by NIH