Effect of heparin on proliferation and signalling in BC3H-1 muscle cells. Evidence for specific binding sites |
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Authors: | S Vannucchi F Pasquali G Fiorelli P Bianchini M Ruggiero |
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Institution: | Istiuto di Patologia Generale, University of Firenze, Italy. |
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Abstract: | 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. |
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