The cadmium-induced disruption of tight junctions in LLC-PK1 cells does not result from apoptosis.
Exposure of LLC-PK1 cells to low micromolar concentrations of Cd2+ for 1-4 hours causes the disruption of the adhering and occluding junctions between the cells, whereas exposure to higher concentrations of Cd2+ for longer periods of time causes more severe toxic effects and cell death. The objective of the present studies was to determine whether or not the junctional effects of Cd2+ might be a consequence of apoptotic injury. LLC-PK1 cells on cell culture inserts were exposed to either Cd2+ or tumor necrosis factor (TNF-alpha) plus cycloheximide, a treatment that has recently been shown to cause apoptosis in LLC-PK1 cells. The results showed that at the time the Cd2(+)-induced junctional changes were occurring, there was no increase in the number of apoptotic cells or evidence of DNA fragmentation. By contrast, TNF-alpha plus cycloheximide induced changes that were characteristic of apoptosis. These results indicate that the disruption of intercellular junctions by Cd2+ in the LLC-PK1 cell line occurs independently of apoptosis.
Prozialeck
W C
WC
Department of Pharmacology, Midwestern University, Downers Grove, IL 60515, USA.
Wellington
D R
DR
Mosher
T L
TL
Lamar
P C
PC
Laddaga
R A
RA
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002104:Cadmium / Q000494:pharmacology*; D002460:Cell Line; D007365:Intercellular Junctions / Q000187:drug effects*; D018374:LLC-PK1 Cells / Q000166:cytology / Q000187:drug effects*; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D014409:Tumor Necrosis Factor-alpha; D002104:Cadmium