Effect of heparin on proliferation and signalling in BC3H-1 muscle cells. Evidence for specific binding sites.
We studied binding and growth inhibitory properties of different glycosaminoglycans in growing and differentiated BC3H-1 muscle cells. Heparin (10 micrograms/ml) and heparan sulfate (10 micrograms/ml) significantly inhibited DNA synthesis in growing and differentiated cells, as monitored by [3H]thymidine incorporation. Binding of heparin to BC3H-1 cells was specific and time-dependent. Heparan sulfate was the only glycosaminoglycan able to displace [3H]heparin (IC50, 3.2 x 10(-7) M), although it was 10-fold less effective than heparin itself (IC50, 3.6 x 10(-8) M). Scatchard analysis revealed the existence of high-affinity heparin binding sites (Kd, 5 x 10(-8) M). Furthermore, heparin inhibited serum-induced stimulation of inositol lipid turnover. Taken together, these results indicate that heparin inhibits BC3H-1 cell growth by interacting with the cell surface, possibly disrupting the flow of growth factor-related mitogenic signalling.
Vannucchi
S
S
Istiuto di Patologia Generale, University of Firenze, Italy.
Pasquali
F
F
Fiorelli
G
G
Bianchini
P
P
Ruggiero
M
M
D000818:Animals; D001667:Binding, Competitive; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D004261:DNA Replication / Q000187:drug effects; D006025:Glycosaminoglycans / Q000494:pharmacology; D006493:Heparin / Q000378:metabolism / Q000494:pharmacology*; D007294:Inositol / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D009132:Muscles; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects*
D006025:Glycosaminoglycans; D007295:Inositol Phosphates; D011956:Receptors, Cell Surface; C037680:heparin receptor; D007294:Inositol; D006493:Heparin