Figure 164

Cell culture models of tight junction disruption and reassembly. The disruption of the permeability barrier, mediated by the tight junction, is a key lesion in the pathogenesis of tubular dysfunction after ischemia and reperfusion. Cell culture models employing ATP depletion and repletion protocols are a commonly used approach for understanding the molecular mechanisms underlying tight junction dysfunction in ischemia and how tight junction integrity recovers after the insult [6, 12, 42]. After short-term ATP depletion (1 hour or less) in Madin-Darby canine kidney cells, although some new synthesis probably occurs, by and large it appears that reassembly of the tight junction can proceed with existing (disassembled) components after ATP repletion. This model of short-term ATP depletion-repletion is probably most relevant to transient sublethal ischemic injury of renal tubule cells. However, in a model of longterm ATP depletion (2.5 to 4 hours), that probably is most relevant to prolonged ischemic (though still sublethal) insult to the renal tubule, it is likely that reestablishment of the permeability barrier (and thus of tubule function) depends on the production (message and protein) and bioassembly of new tight junction components. Many of these components (membrane proteins) are assembled in the endoplasmic reticulum.

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