Regulation of adherens junctions and epithelial paracellular permeability: a novel function for polyamines
| Autor: | Douglas J. Turner, Xin Guo, Lan Liu, Jian Ying Wang, Barbara L. Bass, Tong Tong Zou, Jaladanki N. Rao |
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| Rok vydání: | 2003 |
| Předmět: |
Cell Membrane Permeability
Tight junction Physiology Cadherin Epithelial Cells Adherens Junctions Cell Biology Biology Cadherins Cell junction Epithelium Cell Line Rats Cell biology Adherens junction medicine.anatomical_structure Paracellular transport Catenin Polyamines medicine Animals Calcium Intestinal Mucosa Signal transduction |
| Zdroj: | American Journal of Physiology-Cell Physiology. 285:C1174-C1187 |
| ISSN: | 1522-1563 0363-6143 |
| DOI: | 10.1152/ajpcell.00015.2003 |
| Popis: | Maintenance of intestinal mucosal epithelial integrity requires polyamines that are involved in the multiple signaling pathways controlling gene expression and different epithelial cell functions. Integrity of the intestinal epithelial barrier depends on a complex of proteins composing different intercellular junctions, including tight junctions, adherens junctions, and desmosomes. E-cadherin is primarily found at the adherens junctions and plays a critical role in cell-cell adhesions that are fundamental to formation of the intestinal epithelial barrier. The current study determined whether polyamines regulate intestinal epithelial barrier function by altering E-cadherin expression. Depletion of cellular polyamines by α-difluoromethylornithine (DFMO) reduced intracellular free Ca2+concentration ([Ca2+]cyt), decreased E-cadherin expression, and increased paracellular permeability in normal intestinal epithelial cells (IEC-6 line). Polyamine depletion did not alter expression of tight junction proteins such as zona occludens (ZO)-1, ZO-2, and junctional adhesion molecule (JAM)-1. Addition of exogenous polyamine spermidine reversed the effects of DFMO on [Ca2+]cytand E-cadherin expression and restored paracellular permeability to near normal. Elevation of [Ca2+]cytby the Ca2+ionophore ionomycin increased E-cadherin expression in polyamine-deficient cells. In contrast, reduction of [Ca2+]cytby polyamine depletion or removal of extracellular Ca2+not only inhibited expression of E-cadherin mRNA but also decreased the half-life of E-cadherin protein. These results indicate that polyamines regulate intestinal epithelial paracellular barrier function by altering E-cadherin expression and that polyamines are essential for E-cadherin expression at least partially through [Ca2+]cyt. |
| Databáze: | OpenAIRE |
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