Remodeling of the tight junction during recovery from exposure to hydrogen peroxide in kidney epithelial cells

Jeannette E. Gonzalez, Robert J. DiGeronimo, D'Ann E. Arthur, Jonathan M. King

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

Renal ischemia-reperfusion injury results in oxidative stress-induced alterations in barrier function. Activation of the mitogen-activated protein (MAP) kinase pathway during recovery from oxidative stress may be an effector of oxidant-induced tight junction reorganization. We hypothesized that tight junction composition and barrier function would be perturbed during recovery from oxidative stress. We developed a model of short-term H2O2 exposure followed by recovery using Madin Darby canine kidney (MDCK II) cells. H2O2 perturbs barrier function without a significant cytotoxic effect except in significant doses. ERK-1/2 and p38, both enzymes of the MAP kinase pathway, were activated within minutes of exposure to H2O2. Transient exposure to H2O2 produced a biphasic response in the transepithelial electrical resistance (TER). An initial drop in TER at 6 h was followed by a significant increase at 24 h. Inhibition of ERK-1/2 activation attenuated the increase in TER observed at 24 h. Expression of occludin initially decreased, followed by partial recovery at 24 h. In contrast, claudin-1 levels decreased and failed to recover at 24 h. Claudin-2 levels were markedly decreased at 24 h; however, inhibition of ERK-1/2 activation was protective. Occludin and claudin-1 localization at the apical membrane on immunofluorescence images was fragmented at 6 h after H2O2 exposure with subsequent recovery of appropriate localization by 24 h. MDCK II cell recovery after H2O2 exposure is associated with functional and structural modifications of the tight junction that are mediated in part by activation of the MAP kinase enzymes ERK-1/2 and p38.

Original languageEnglish (US)
Pages (from-to)1561-1569
Number of pages9
JournalFree Radical Biology and Medicine
Volume47
Issue number11
DOIs
StatePublished - Dec 1 2009
Externally publishedYes

Keywords

  • Barrier function
  • Free radicals
  • Kidney epithelium
  • Oxidative stress
  • Tight junction

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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