Potassium-Chloride Cotransporter Mediates Cell Cycle Progression and Proliferation of Human Corneal Epithelial Cells
| Autor: | Pavel Iserovish, José E. Capó-Aponte, M. A. Murat Akinci, J. Mario Wolosin, Peter S. Reinach, Kathryn S. Pokorny, Zheng Wang |
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| Rok vydání: | 2007 |
| Předmět: |
MAPK/ERK pathway
Cell Population Biology Cornea Epidermal growth factor medicine Humans Protein kinase A education Molecular Biology Cell Line Transformed Cell Proliferation Cell Size education.field_of_study Symporters Cell growth Cell Cycle Epithelial Cells Cell Biology Cell cycle Cell biology medicine.anatomical_structure sense organs Cotransporter Developmental Biology |
| Zdroj: | Cell Cycle. 6:2709-2718 |
| ISSN: | 1551-4005 1538-4101 |
| DOI: | 10.4161/cc.6.21.4881 |
| Popis: | Epidermal growth factor (EGF)-induced proliferation of corneal epithelial cells contributes to its renewal, which maintains the protective and refractive properties of the cornea. This study characterized in human corneal epithelial cells (HCEC) the role of the potassium-chloride cotransporter (KCC) in mediating (1) EGF-induced mitogen-activated protein kinase (MAPK) pathway activation; (2) increases in cell cycle progression; and (3) proliferation. The KCC inhibitor [(dihydroindenyl)oxy] alkanoic acid (DIOA) and KCC activator N-ethylmaleimide (NEM), suppressed and enhanced EGF-induced p44/42MAPK activation, respectively. Such selective modulation was mirrored by corresponding changes in cell proliferation and shifts in cell cycle distribution. DIOA induced a 20% increase in G(0)/G(1)-phase cell population, whereas NEM induced a 22% increase in the proportion of cells in the G(2)/M-phase and accelerated the transition from G(0)/G(1)-phase to the S-phase. Associated with these changes, KCC1 content in a plasma membrane enriched fraction increased by 300%. Alterations in regulatory volume capacity were associated with corresponding changes in both KCC1 membrane content and activity. These results indicate that EGF-induced increases in KCC1 activity and content modulate cell volume changes required for (1) activation of the p44/42MAPK signaling pathway, (2) cell cycle progression, and (3) increases in cell proliferation. |
| Databáze: | OpenAIRE |
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