title: Hyperosmotic induction of the mitogen-activated protein kinase phosphatase MKP-1 in H4IIE rat hepatoma cells.
abstract: The action of hyperosmotic stress on the MAP kinase phosphatase MKP-1 mRNA expression was studied in H4IIE rat hepatoma cells. Hyperosmotic (405 mosmol/L) challenge of the cells led to a transient expression of MKP-1 mRNA, which was maximal after 6-8 h and disappeared completely after 24 h. Hyperosmotic MKP-1 mRNA induction was preceded by a transient activation of the MAP kinases Erk-1, Erk-2, and JNK-2, which were not prerequisite for MKP-1 mRNA accumulation. However, the hyperosmolarity-induced MKP-1 mRNA expression was sensitive to antioxidants and to inhibition of p38 by SB203580. A reduced sensitivity of Erk-1/Erk-2 to other stimuli was found after prolonged hyperosmotic exposure. The data are consistent with a hyperosmolarity-induced MKP-1 expression via reactive oxygen intermediates and p38, which may participate in the termination of MAP kinase activation and contribute to desensitization of the MAP kinases after prolonged hyperosmotic exposure of the cells.
authors.affiliation: Clinic for Gastroenterology, Hepatology, and Infectiology, Heinrich-Heine-Universität, Düsseldorf, Germany. Freimut.Schliess@uni-duesseldorf.de
authors.forename: F
authors.initials: F
authors.lastname: Schliess
authors.forename: S
authors.initials: S
authors.lastname: Heinrich
authors.forename: D
authors.initials: D
authors.lastname: Häussinger
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D018797:Cell Cycle Proteins; D054638:Dual Specificity Phosphatase 1; D004789:Enzyme Activation; D004790:Enzyme Induction; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression; D007093:Imidazoles / Q000494:pharmacology; D017874:Immediate-Early Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D048031:JNK Mitogen-Activated Protein Kinases; D007700:Kinetics; D008114:Liver Neoplasms, Experimental / Q000201:enzymology*; D048670:MAP Kinase Kinase 4; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D010749:Phosphoprotein Phosphatases; D011494:Protein Kinases / Q000378:metabolism; D054645:Protein Phosphatase 1; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D012462:Saline Solution, Hypertonic; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D000975:Antioxidants; D018797:Cell Cycle Proteins; D004791:Enzyme Inhibitors; D007093:Imidazoles; D017874:Immediate-Early Proteins; D011725:Pyridines; D012333:RNA, Messenger; D012462:Saline Solution, Hypertonic; D011494:Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D054638:Dual Specificity Phosphatase 1; C517021:Dusp1 protein, rat; D017027:Protein Tyrosine Phosphatases; C093642:SB 203580