Binding of heparin and compound Y to endothelial cells stimulates the synthesis of an antithrombotic heparan sulfate proteoglycan.
The mechanism by which heparin and antithrombotic agents, including a cyclic octaphenolsulfonic acid (compound Y), stimulate the synthesis of an antithrombotic heparan sulfate by endothelial cells in culture was investigated. Compound Y increases the amount of heparan sulfate from the cell surface and secreted to the medium by endothelial cells by three-fold. Binding experiments have shown saturation of the endothelial cell receptors at a concentration of 0.16 microM for heparin and 2.7 microM for compound Y. The kinetic binding constants (Ks) for compound Y and heparin were 1,333 nM and 42 nM, respectively. It was also shown that both compounds bind to the same receptors. The Scatchard plots indicated that 1,319 nmoles compound Y and 35 nmoles heparin bound per microgram cell protein, indicating that 40-fold more molecules of compound Y bound to the receptors when compared to heparin. No significant internalization of the compounds was observed.
Pinhal
M A
MA
Departamento de Bioquímica, Escola Paulista de Medicina, São Paulo, Brasil.
Silva
I F
IF
Lee
T C
TC
Dietrich
C P
CP
Nader
H B
HB
D000818:Animals; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006168:Guinea Pigs; D019812:Heparan Sulfate Proteoglycans; D006493:Heparin / Q000378:metabolism*; D006497:Heparan Sulfate / Q000096:biosynthesis*; D011485:Protein Binding; D011509:Proteoglycans / Q000096:biosynthesis*; D011817:Rabbits; D013451:Sulfonic Acids / Q000378:metabolism*; D013997:Time Factors
D019812:Heparan Sulfate Proteoglycans; D006493:Heparin; D006497:Heparan Sulfate; D011509:Proteoglycans; D013451:Sulfonic Acids