FUNCTIONAL AND CYTOSKELETAL CHANGES INDUCED BY SUBLETHAL INJURY IN PROXIMAL TUBULAR EPITHELIAL-CELLS

Mouse proximal tubular (MPT) cells in culture were subjected to ATP de pletion by incubating them with cyanide in the absence of dextrose for 1 h. This insult resulted in marked alterations in the actin cytoskel eton. These changes were not associated with a decrease in cell viabil ity and thus reflected sublethal injury. The effect of sublethal injur y on the functional integrity of the intercellular tight junction (TJ) was then examined in MPT cell monolayers grown on permeable supports. During chemical anoxia, monolayer permeability to the paracellular ma rker mannitol progressively increased to 297 +/- 62% of baseline after 1 h. Chemical anoxia also caused a reversible loss in cell-substrate adhesion when MPT cells were studied as confluent monolayers or as sin gle cells. Thus disruption of the actin cytoskeleton in nonlethally in jured cells results in important reversible alterations in renal epith elial function characterized by impairment of the ''gate'' function of the TJ as well as impaired cell-substrate adhesion. We hypothesize th at sublethal epithelial cell injury without accompanying necrosis may contribute to the decrement in renal function characteristic of ischem ic renal injury.