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 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.
Department of Internal Medicine Clinic for Gastroenterology, Hepatology, and Infectiology, Heinrich-Heine-Universität, Düsseldorf, Germany.
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Wiese
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Schliess
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Häussinger
D000818:Animals; D015152:Blotting, Northern; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D009997:Osmotic Pressure; D051381:Rats; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D014638:Vanadates / Q000378:metabolism*
D014638:Vanadates; D017871:Calcium-Calmodulin-Dependent Protein Kinases