Ischemia-induced cleavage of cadherins in NRK cells is not sufficient for beta-catenin transcriptional activity. Academic Article uri icon

abstract

  • Although ischemia is associated with disruption of cadherin-mediated adhesion in renal cell lines, the impact of decreased cadherin function on the transcriptional activity of beta-catenin remains poorly defined. In these studies, we used a simulated ischemia model in normal rat kidney (NRK) cells to disrupt cadherin function. Cell viability; cadherin/catenin expression, function, and localization; and beta-catenin-mediated transcriptional activity were assessed during ischemia/reperfusion. Following 6 hr of ischemia, a decrease in the expression of E- and N-cadherin was seen that correlated with altered cell morphology indicative of decreased intercellular adhesion. While ischemia was associated with activation of glycogen synthase kinase 3 beta (GSK-3beta), this did not correlate with increased phosphorylation of beta-catenin as assessed by Western blots using phosphoryl-specific antibodies. beta-Catenin was not localized to the nucleus by immunofluorescence in ischemic NRK cells, but rather a strong perinuclear signal was seen in reperfused cells. This was consistent with the finding that neither ischemia nor reperfusion activated the transcriptional activity of beta-catenin as assessed by the TCF-optimal promoter (TOPFlash) construct. However, NRK cells possess a competent Wnt pathway, as challenge with lithium chloride elicited a ten-fold increase in luciferase activity. These results suggest that ischemia-induced disruption of cadherin/catenin complexes is not sufficient to stimulate beta-catenin transcriptional activity in NRK cells.

published proceedings

  • Cell Commun Adhes

author list (cited authors)

  • Chen, G., Akintola, A. D., Catania, J. M., Covington, M. D., Dean, D. D., Trzeciakowski, J. P., Burghardt, R. C., & Parrish, A. R.

citation count

  • 4

complete list of authors

  • Chen, Gang||Akintola, Adebayo D||Catania, Jeffrey M||Covington, Marisa D||Dean, Dana D||Trzeciakowski, Jerome P||Burghardt, Robert C||Parrish, Alan R

publication date

  • October 2007