Inhibitors of glycosphingolipid biosynthesis reduce transepithelial electrical resistance in MDCK I and FRT cells.
Madin-Darby canine kidney (MDCK) I and Fisher rat thyroid (FRT) cells exhibit transepithelial electrical resistance (TER) values in excess of 5,000 Omega. cm(2). When these cells were incubated in the presence of various inhibitors of sphingolipid biosynthesis, a >5-fold reduction of TER was observed without changes in the gate function for uncharged solutes or the fence function for apically applied fluorescent lipids. The localization of ZO-1 and occludin was not altered between control and inhibitor-treated cells, indicating that the tight junction was still intact. Furthermore, the complexity of tight junction strands, analyzed by freeze-fracture microscopy, was not reduced. Once the inhibitor was removed and the cells were allowed to synthesize sphingolipids, a gradual recovery of the TER was observed. Interestingly, these inhibitors did not attenuate the TER of MDCK II cells, a cell line that typically exhibits values below 800 omega x cm(2.) These results suggest that glycosphingolipids play a role in regulating the electrical properties of epithelial cells.
Leung
Lawrence W
LW
Margaret M. Dyson Vision Research Institute, Weill Medical College of Cornell University, New York, New York 10021, USA.
Contreras
Ruben G
RG
Flores-Maldonado
Catalina
C
Cereijido
Marcelino
M
Rodriguez-Boulan
Enrique
E
D000818:Animals; D002460:Cell Line; D062465:Claudin-3; D057167:Claudins; D004285:Dogs; D004537:Eicosanoic Acids / Q000494:pharmacology; D017097:Electric Impedance; D004847:Epithelial Cells / Q000502:physiology; D037341:Fumonisins / Q000494:pharmacology; D006028:Glycosphingolipids / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D007668:Kidney / Q000166:cytology / Q000502:physiology*; D008055:Lipids / Q000737:chemistry; D008565:Membrane Proteins / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D017434:Protein Structure, Tertiary / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D013107:Sphingolipids / Q000494:pharmacology; D013961:Thyroid Gland / Q000166:cytology / Q000502:physiology*; D019108:Tight Junctions / Q000187:drug effects / Q000502:physiology
C095823:1-phenyl-2-palmitoylamino-3-morpholino-1-propanol; D062465:Claudin-3; D057167:Claudins; C491874:Cldn2 protein, rat; C568124:Cldn3 protein, rat; D004537:Eicosanoic Acids; D037341:Fumonisins; D006028:Glycosphingolipids; D008055:Lipids; D008565:Membrane Proteins; D009025:Morpholines; D013107:Sphingolipids; C087464:mycestericin C; C056933:fumonisin B1