Role of protein tyrosine phosphorylation in acetaldehyde-induced disruption of epithelial tight junctions. American Journal of Physiology
Acetaldehyde-induced cytotoxicity is an important factor in pathogenesis of alcohol-related diseases; however, the mechanism of this toxicity is unknown. We recently showed that acetaldehyde increases epithelial paracellular permeability. We asked whether protein tyrosine phosphorylation via modulation of tyrosine kinases and/or PTPases is a mechanism involved in acetaldehyde-induced disruption of the tight junctions in the Caco-2 cell monolayer. Immunofluorescence localization of occludin and ZO-1 showed disruption of the tight junctions in acetaldehyde-treated cell monolayer. Administration of genistein prevented acetaldehyde-induced permeability. Acetaldehyde increased tyrosine phosphorylation of three clusters of proteins with molecular masses of 30-50, 60-90, and 110-150 kDa; three of these proteins were ZO-1, E-cadherin, and beta-catenin. Acetaldehyde reduced PTPase activity in plasma membrane and soluble fractions, whereas tyrosine kinase activity remained unaffected. Treatment with acetaldehyde resulted in a 97% loss of protein tyrosine phosphatase (PTP)1B activity and a partial reduction of PTP1C and PTP1D activities. These results strongly suggest that acetaldehyde inhibits PTPases to increase protein tyrosine phosphorylation, which may result in disruption of the tight junctions.
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.