Osmotic regulation of MAP-kinase activities and gene expression in H4IIE rat hepatoma cells

The effects of hypo- and hyper-osmotic shock on endogenous MAP-kinase activities and MKP-1 and c-jun mRNA levels were studied in H411E rat hepatoma cells, In presence of vanadate hypo-osmolarity stimulated a rapid and sustained activation of MAP-kinases (Erk-2, JNK-2 and p38). In the absence of vanadate a hypoosmotic MAP-kinase response was not detectable. Hyper-osmolarity stimulated a delayed and transient MAP-kinase activation and vanadate was not required for its detection. Vanadate, however, amplified the hyper-osmotic MAP-kinase stimulation, c-jun and MKP-1 mRNA levels were maximal after 0.5 -1 h of hypoosmotic exposure and returned towards basal levels within 2 h, whereas the hyper-osmotic induction of c-jun and MKP-1 mRNA was delayed. Vanadate was not required for the anise-osmotic effects on MKP-1 and c-jun mRNA levels. Whereas the hyper-osmolarity-induced c-jun mRNA accumulation returned towards basal levels within 8 h, MKP-1 mRNA was still highly expressed at this time point. The role of MAP-kinases for the induction of aniso-osmolarity-induced gene expression and the potential importance of MKP-1 for termination of anise-osmotic MAP-kinase activation are discussed.