Antithrombin III modulates the effect of thrombin on the metabolism of glycosaminoglycans in cultured endothelial cells.
We previously reported that a treatment of cultures of endothelial cells from bovine aorta with thrombin resulted in a less accumulation of glycosaminoglycans (GAG) in the cell layer. In the present study, we found that thrombin-induced decrease in the accumulation of [35S]sulfate-labeled GAG (35S-GAG) such as heparan sulfate was prevented by antithrombin III (AT III) but not by heparin cofactor II (HC II). However, AT III did not show a significant effect on the 35S-GAG accumulation individually. Pretreatment of the cell layer with neither AT III nor HC II showed any preventive effect. When GAG in the cell layer was labeled with both [35S]sulfate and [3H]glucosamine, neither thrombin nor a combination of thrombin with AT III changed the ratio of the radioactivity of 35S to that of 3H. Although thrombin stimulated the release of 35S-GAG from the cell layer, AT III completely prevented the stimulatory effect. In conclusion, it was suggested that AT III may inhibit the thrombin action on GAG metabolism of endothelial cells to prevent thrombosis in vivo.
Akai
T
T
Department of Neurosurgery, Faculty Medicine, Toyama Medical and Pharmaceutical University, Japan.
Kaji
T
T
Hayakawa
Y
Y
Hayashi
T
T
Sakuragawa
N
N
D000818:Animals; D000990:Antithrombin III / Q000494:pharmacology*; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism*; D015844:Heparin Cofactor II / Q000494:pharmacology; D006497:Heparan Sulfate / Q000378:metabolism; D013917:Thrombin / Q000037:antagonists & inhibitors*
D000990:Antithrombin III; D006025:Glycosaminoglycans; D015844:Heparin Cofactor II; D006497:Heparan Sulfate; D013917:Thrombin