Hypo-osmotic cell swelling activates the p38 MAP kinase signalling cascade.
Hypo-osmotic swelling of human Intestine 407 cells leads to a significant increase of intracellular MAPKAP-kinase 2 activity and Hsp27 phosphorylation. Pre-treatment of the cells with the p38 MAP kinase inhibitor SB-203580 blocks this activation, indicating that the hypotonicity-induced activation of MAPKAP kinase 2 is, similarly to that described for hyperosmotic treatment, the result of an activated p38 MAP kinase cascade. The activation of MAPKAP kinase 2 proceeds with kinetics similar to that of one of the first physiological responses of hypo-osmotic treatment, the opening of compensatory Cl- channels. However, inhibition of the p38 MAP kinase cascade does not block the osmo-sensitive anion efflux and, vice versa, activation of p38 MAP kinase by cytokines and anisomycin does not increase the efflux. These results indicate that the p38 MAP kinase cascade is not directly involved in Cl- channel activation but instead may play a role in subsequent cellular repair processes.
Department of Biochemistry, Cardiovascular Research Institute COEUR, Faculty of Medicine and Health Sciences, Erasmus University, Rotterdam, The Netherlands. tilly@bc1.fgg.eur.nl
B C
BC
Tilly
M
M
Gaestel
K
K
Engel
M J
MJ
Edixhoven
H R
HR
de Jonge
D000841:Anisomycin / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002460:Cell Line; D018118:Chloride Channels / Q000187:drug effects / Q000502:physiology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D007038:Hypotonic Solutions; D007375:Interleukin-1 / Q000494:pharmacology; D007422:Intestines; D047908:Intracellular Signaling Peptides and Proteins; D007454:Iodides / Q000378:metabolism; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases; D000099190:MAP-Kinase-Activated Kinase 2
D000841:Anisomycin; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D018118:Chloride Channels; D004791:Enzyme Inhibitors; D006360:Heat-Shock Proteins; D007038:Hypotonic Solutions; D007375:Interleukin-1; D047908:Intracellular Signaling Peptides and Proteins; D007454:Iodides; D008070:Lipopolysaccharides; D020928:Mitogen-Activated Protein Kinases; D017346:Protein Serine-Threonine Kinases; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases; D000099190:MAP-Kinase-Activated Kinase 2