Plasmin-induced reduction of heparan sulfate in cultured vascular endothelial cell layer.
Plasmin-induced alteration of glycosaminoglycans (GAGs) was investigated using a cell culture system of vascular endothelial cells derived from bovine aorta. In the cell layer, the incorporation of [3H]glucosamine into GAGs, a marker of the sugar chain formation, was slightly decreased by plasmin. On the other hand, the incorporation of [35S]sulfate, a marker of the sulfation, was markedly decreased by the protease. Plasminogen also induced a weak but similar change. Characterization of the cellular GAGs showed that plasmin inhibited the incorporation of both [3H]glucosamine and [35S]sulfate into the major component heparan sulfate at a similar degree. In the other GAGs, the [35S]sulfate incorporation was significantly decreased by plasmin without a change of the [3H]glucosamine incorporation. The leakage of lactate dehydrogenase from the endothelial cells was significantly increased by plasmin, suggesting that the protease exhibited cytotoxicity. The present data suggest that the anticoagulant activity on the surface of vascular endothelium mediated by the anticoagulant heparan sulfate may be reduced by plasmin which will be generated from plasminogen by plasminogen activators derived from endothelial cells.
Department of Environmental Science, Faculty of Pharmaceutical Sciences, Hokuriku University, Japan.
T
T
Kaji
S
S
Hiraga
N
N
Fujii
C
C
Yamamoto
M
M
Sakamoto
H
H
Kozuka
F
F
Koizumi
D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005341:Fibrinolysin / Q000494:pharmacology*; D006497:Heparan Sulfate / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D010084:Oxidation-Reduction
D005341:Fibrinolysin; D006497:Heparan Sulfate; D007770:L-Lactate Dehydrogenase