Functional and morphological changes induced by tunicamycin in dividing and confluent endothelial cells.
Cultured bovine aortic endothelial cells treated with tunicamycin, an inhibitor of glycoprotein synthesis, developed a concentration-dependent inhibition of N-acetylglucosamine-1-phosphate transferase activity, and this inhibition was correlated with a substantial decrease in [3H]mannose incorporation by the cells. Endothelial cells were very sensitive to tunicamycin, and changes in their morphology occurred as a result of the inhibition of glycoprotein synthesis. The cells became elongated, the surface irregular, roughened, and granular, and there was an increase in the interstitial space between the cells. Electron dense material was accumulated within and dilated the rough endoplasmic reticulum, and the distribution of the glycoproteins laminin and fibronectin throughout the endothelial cell monolayer was modified. These morphological changes coincided with functional impairment with the permeability of endothelial cell monolayers to both 125I-albumin and [3H]inulin being increased by treatment with tunicamycin (10(-6) M) for 24 h. These results indicate that the synthesis of glycoproteins is crucial for cell-cell adhesion and the functional properties of the endothelial lining of blood vessels.
Tiganis
T
T
Department of Pharmacology, University of Melbourne, Victoria, Australia.
Leaver
D D
DD
Ham
K
K
Friedhuber
A
A
Stewart
P
P
Dziadek
M
M
D000418:Albumins / Q000378:metabolism; D000818:Animals; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000648:ultrastructure; D006023:Glycoproteins / Q000502:physiology*; D007124:Immunoenzyme Techniques; D007444:Inulin / Q000378:metabolism; D007930:Leucine / Q000378:metabolism; D008358:Mannose / Q000378:metabolism; D008854:Microscopy, Electron; D010770:Phosphotransferases / Q000037:antagonists & inhibitors / Q000378:metabolism; D017855:Transferases (Other Substituted Phosphate Groups); D014415:Tunicamycin / Q000494:pharmacology*
D000418:Albumins; D006023:Glycoproteins; D014415:Tunicamycin; D007444:Inulin; D010770:Phosphotransferases; D017855:Transferases (Other Substituted Phosphate Groups); C030012:UDP-N-acetylglucosamine-lysosomal-enzyme-N-acetylglucosaminephosphotransferase; D007930:Leucine; D008358:Mannose