| Autor: |
King, Jonathan M., Gonzalez, Jeannette E., Arthur, D'Ann E., Derickson, Darcy L. |
| Předmět: |
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| Zdroj: |
FASEB Journal; Apr2007, Vol. 21 Issue 5, pA452-A452, 1/5p |
| Abstrakt: |
Oxidative stress has been linked to many disease processes, including ischemia-reperfusion injury and toxicant damage. Loss of barrier function in renal epithelial cells due to alterations in the tight junction (TJ) may complicate the effects of oxidative stress. The mitogen-activated protein kinase (MAPK) pathway has been shown to be an early cellular signal during hydrogen peroxide exposure oxidant injury and may be linked to TJ protein alterations. In this study, we are interested in effects on cell barrier function due to a brief exposure to hydrogen peroxide and the ensuing recovery period. Transepithelial electrical resistance and paracellular flux were used as a measure of barrier integrity, while the lactate dehydrogenase activity assay was used to assess cytotoxicity. Protein expression was determined via Western blot analysis, and immunofluorescent staining was used for localization of TJ proteins and examination of the actin cytoskeleton. A positive relationship between dose of hydrogen peroxide and cytotoxicity was observed. Low doses of hydrogen peroxide perturb TJ function without exhibiting a cytotoxic effect. ERK-1/2, an enzyme of the MAPK pathway, was activated within minutes of exposure to hydrogen peroxide as determined by phospho-ERK content. Exposure to hydrogen peroxide with subsequent recovery was also associated with changes in expression and localization of the TJ proteins occludin and claudin-1. These findings demonstrate that the TJ in MDCK cells is altered by exposure to hydrogen peroxide and these changes are preceded by activation of the MAPK pathway. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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