Cadmium-induced alteration of glycosaminoglycans with an enhancement of heparin-like activity in cultured vascular endothelial cells.
Glycosaminoglycans (GAGs), especially heparan sulfate, are involved in the anticoagulant property of vascular endothelium. It was observed that heparin-like activity on the surface of cultured bovine aortic endothelial cells was enhanced by cadmium at 1.0 microM or more after a 24-h incubation. The incorporation of [3H]glucosamine into GAGs, a marker of GAG synthesis, was markedly increased by cadmium at 0.5 microM or more in both the cell layer and the conditioned medium; however, the incorporation of [35S]sulfate, a marker of the GAG sulfation, was significantly reduced by the metal at 2.0 microM or more. Similar changes were observed in a cultured human umbilical vein endothelial cell layer. Characterization of GAGs in bovine endothelial cell layer revealed that cadmium (2.0 microM)-induced alterations mostly occurred in the major component heparan sulfate rather than in other minor GAGs. Stimulation of [3H]glucosamine incorporation by cadmium at 2.0 microM occurred even in the presence of p-nitrophenyl-beta-D-xyloside but disappeared in the presence of cycloheximide, suggesting that cadmium might induce the production of proteins which are involved in GAG synthesis. The present data suggest that vascular endothelial cells are capable of enhancing the potential anticoagulant activity on their surface via induction of heparan sulfate synthesis. This response of endothelial cells may be a defensive one to the procoagulant state of blood which can be induced by cadmium.
Kaji
T
T
Department of Environmental Science, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
Ohkawara
S
S
Yamamoto
C
C
Sakamoto
M
M
Kozuka
H
H
D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D002104:Cadmium / Q000494:pharmacology*; D002417:Cattle; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005944:Glucosamine / Q000378:metabolism; D006025:Glycosaminoglycans / Q000096:biosynthesis*; D006497:Heparan Sulfate / Q000096:biosynthesis*; D006801:Humans
D002104:Cadmium; D005944:Glucosamine; D006025:Glycosaminoglycans; D006497:Heparan Sulfate