Pathophysiology and functional significance of apical membrane disruption during ischemia

S. L. Ashworth, B. A. Molitoris

Research output: Contribution to journalReview article

30 Scopus citations

Abstract

The characteristic structure of polarized proximal tubule cells is drastically altered by the onset of ischemic acute renal failure. Distinctive apical brush border microvilli disruption occurs rapidly and in a duration- dependent fashion. Microvillar membranes internalize into the cytosol of the cell or are shed into the lumen as blebs. The microvillar actin core disassembles concurrent with or preceding these membrane changes. Actin and its associated binding proteins no longer interact to form these highly regulated apical membrane structures necessary for microvilli. The resultant epithelial cells have a reduced apical membrane surface that is not polarized either structurally, biochemically or physiologically. Furthermore, the changes in the apical microvilli result in tubular obstruction, reduced Na+ absorption, and partly explain the reduction in glomerular filtration rate. Recent evidence suggests these actin surface membrane alterations induced by ischemia are secondary to activation and relocation of the actin-associated protein, actin depolymerizing factor/cofilin, to the apical membrane domain. Activated (dephosphorylated) actin depolymerizing factor/cofilin proteins bind filamentous actin, increasing subunit treadmilling rates and filament severing. Once activated, the diffuse cytoplasmic distribution of the actin depolymerizing factor/cofilin protein relocalizes to the luminal membrane blebs. During recovery the actin depolymerizing factor/cofilin proteins are again phosphorylated and reassume their normal diffuse cytoplasmic localization. This evidence strongly supports the hypothesis that actin depolymerizing factor/cofilin proteins play a significant role in ischemia- induced injury in the proximal tubule cells.

Original languageEnglish (US)
Pages (from-to)449-458
Number of pages10
JournalCurrent Opinion in Nephrology and Hypertension
Volume8
Issue number4
DOIs
StatePublished - Dec 1 1999

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ASJC Scopus subject areas

  • Internal Medicine
  • Nephrology

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