Functional and cytoskeletal changes induced by sublethal injury in proximal tubular epithelial cells.
Mouse proximal tubular (MPT) cells in culture were subjected to ATP depletion by incubating them with cyanide in the absence of dextrose for 1 h. This insult resulted in marked alterations in the actin cytoskeleton. These changes were not associated with a decrease in cell viability and thus reflected sublethal injury. The effect of sublethal injury 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 marker 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 single cells. Thus disruption of the actin cytoskeleton in nonlethally injured cells results in important reversible alterations in renal epithelial function characterized by impairment of the "gate" function of the TJ as well as impaired cell-substrate adhesion. We hypothesize that sublethal epithelial cell injury without accompanying necrosis may contribute to the decrement in renal function characteristic of ischemic renal injury.
Kroshian
V M
VM
Evans Memorial Department of Clinical Research, Boston University Medical Center, University Hospital, Massachusetts 02118.
Sheridan
A M
AM
Lieberthal
W
W
D000199:Actins / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002470:Cell Survival; D002478:Cells, Cultured; D003486:Cyanides; D015638:Cytochalasin D / Q000494:pharmacology; D003599:Cytoskeleton / Q000378:metabolism* / Q000648:ultrastructure*; D000860:Hypoxia / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology*; D007365:Intercellular Junctions / Q000502:physiology; D007687:Kidney Tubules, Proximal / Q000378:metabolism / Q000473:pathology* / Q000502:physiology*; D008353:Mannitol / Q000493:pharmacokinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D010539:Permeability
D000199:Actins; D003486:Cyanides; D015638:Cytochalasin D; D008353:Mannitol; D000255:Adenosine Triphosphate