Ouabain inhibits p38 activation in thymocytes

The MAPK p38 is phosphorylated by multiple stimuli and regulates a number of transcription factors. It is reported that activation of p38 leading to the regulation of NFAT may result from an alternative MKK-independent mechanism. This alternative pathway involves the protein Dlgh1 as an essential scaffold that assembles a module for the activation of p38. Ouabain, a specific inhibitor of the Na+/K+-ATPase, is capable of inducing the activation of various signal transduction cascades. In the present work, P-p38 levels of ConA-activated thymocytes treated with ouabain (1, 10 and 100 nM) were measured as also the effect of ouabain on NFATc1 expression. p38 phosphorylation and NFATc1 levels were analyzed by flow cytometry. The results indicated that ouabain inhibited both ConA-dependent increase in P-p38 and NFATc1 levels, which suggests an effect of ouabain on the p38 alternative pathway.