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

Biol Chem. 1998 Jun;379(6):667-71. doi: 10.1515/bchm.1998.379.6.667.


The effects of hypo- and hyper-osmotic shock on endogenous MAP-kinase activities and MKP-1 and c-jun mRNA levels were studied in H4IIE 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 hypo-osmotic 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 hypo-osmotic 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 aniso-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 aniso-osmotic MAP-kinase activation are discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Northern
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Carcinoma, Hepatocellular / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Liver Neoplasms, Experimental / metabolism*
  • Osmotic Pressure
  • Rats
  • Signal Transduction*
  • Tumor Cells, Cultured
  • Vanadates / metabolism*


  • Vanadates
  • Calcium-Calmodulin-Dependent Protein Kinases