Effects of acute vs. chronic phorbol ester exposure on transepithelial permeability and epithelial morphology
| Autor: | Lisa Misner, Thomas G. O'Brien, James M. Mullin, Robert D. Shurina, Shotaro Imaizumi, Jasna Noe, Kathleen V. Snock, Kenneth D. George |
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| Rok vydání: | 1992 |
| Předmět: |
medicine.medical_specialty
Cell Membrane Permeability Time Factors Physiology Immunoblotting Clinical Biochemistry Cell Epithelium Kidney Tubules Proximal Cell–cell interaction Internal medicine Phorbol Esters medicine Animals Cells Cultured Protein Kinase C Protein kinase C Tight junction Chemistry Epithelial Cells Cell Biology Enzyme Activation Microscopy Electron Cytosol Intercellular Junctions medicine.anatomical_structure Endocrinology Permeability (electromagnetism) Paracellular transport |
| Zdroj: | Journal of Cellular Physiology. 152:35-47 |
| ISSN: | 1097-4652 0021-9541 |
| DOI: | 10.1002/jcp.1041520106 |
| Popis: | In previous experiments we have shown that acute (30 minutes) exposure to phorbol esters or other protein kinase C activators causes increased transepithelial permeability, specifically by the increased paracellular permeability through tight junctions. However, the role of protein kinase C activators in carcinogenesis is predicted upon a chronic exposure of an effective dose at frequent intervals for a prolonged period of time. We therefore sought to determine the effect of chronic phorbol ester exposure on transepithelial permeability by exposing cells of the polar renal epithelial cell line, LLC-PK1, to phorbol esters for time periods as long as 16 weeks. The following changes ensued: (1) after the initial drop in transepithelial resistance due to phorbol ester exposure, i.e., an increase in transepithelial permeability (in the acute phase of exposure), an adaptive response occurs as transepithelial resistances in chronically exposed cultures recover to approximately 50% of control values, (2) the cell sheets in chronically exposed cultures lose their acute responsiveness of transepithelial permeability to phorbol ester exposure, (3) cell sheet architecture changes as cells occasionally multilayer and actual polyp-like cell masses appear at high frequency, and (4) cytosolic protein kinase C activity decreases to 50% of control level with acute exposure and then is further decreased to less than 1% of control level in chronically treated cells; membrane-associated PKC activity is not as sharply decreased. The possible role of transepithelial permeability in carcinogenesis and the value of chronically treated epithelial cell cultures as a model for two-stage carcinogenesis are discussed. © 1992 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
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