Low-dose exposure of intestinal epithelial cells to formaldehyde results in MAP kinase activation and molecular alteration of the focal adhesion protein paxillin.
We investigated the potential pathophysiological role of non-lethal formaldehyde concentrations on human intestinal epithelial HT-29 cells. Expression levels of actin, tubulin and detectable cytokeratin isoforms 5, 13, 18, 19 and 20 were not affected after 24h of exposure to 1mM formaldehyde. By contrast, cellular organization of cytoskeletal constituents was already changed after 60 min. Within 15 min, formaldehyde induced profound tyrosine phosphorylation of the focal adhesion protein paxillin and of proteins at about 120-130 kDa. Concomitantly, phosphorylation of ERK-1/2 and p38 MAP kinase occurred. Paxillin was not only tyrosine phosphorylated but underwent a sustained molecular weight shift representing serine/threonine phosphorylation that was independent of MAP kinase activity and EGF-R-mediated signalling. Our data show that exposure of intestinal epithelial cells to low-dose formaldehyde is followed by rapid and profound signalling events. The data suggest a modifier role of environmental or endogenous formaldehyde for epithelial cell functions.
Feick
Peter
P
Department of Medicine II (Gastroenterology/Hepatology/Infectious Diseases), Centre of Environmental Medicine, Medical Faculty of Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany.
Haas
Stephan R L
SR
Singer
Manfred V
MV
Böcker
Ulrich
U
D000469:Alkaline Phosphatase / Q000737:chemistry; D015153:Blotting, Western; D003599:Cytoskeleton / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005557:Formaldehyde / Q000633:toxicity*; D019073:HT29 Cells; D006801:Humans; D047468:Immunoprecipitation; D008856:Microscopy, Fluorescence; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D051419:Paxillin / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013912:Threonine / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D051419:Paxillin; D005557:Formaldehyde; D013912:Threonine; D014443:Tyrosine; D012694:Serine; D048049:Extracellular Signal-Regulated MAP Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D000469:Alkaline Phosphatase