Importance of 2-O-sulfate groups of uronate residues in heparin for activation of FGF-1 and FGF-2.
Complete drying of heparin with various concentrations of NaOH by lyophilization caused specific 2-O-desulfation to various degrees without detectable depolymerization or other chemical changes. In order to assess the importance of 2-O-sulfate groups in uronate residues to promote FGF-1 and FGF-2 activities, various 2-O-desulfated (2-O-DS-) heparins were quantitatively examined for their effects on FGF-1 and FGF-2-induced proliferation of BALB/c3T3 clone A31 (A31) cells and the chlorate-treated cells. Twenty-seven percent or less loss to the 2-O-sulfate groups had no effect on the ability to activate both FGF-1 and FGF-2, while 44% loss resulted in a significant loss of the ability. Complete loss of the ability was observed in 2-O-DS-heparins with 75% or more 2-O-desulfation. These results suggest that a high content of 2-O-sulfate groups in uronate residues of heparin is required for activation of both FGF-1 and FGF-2.
Ishihara
M
M
National Defense Medical College, Research Institute, Saitama.
Kariya
Y
Y
Kikuchi
H
H
Minamisawa
T
T
Yoshida
K
K
D016475:3T3 Cells; D000818:Animals; D019556:COS Cells; D002455:Cell Division; D002704:Chlorates / Q000494:pharmacology; D002999:Clone Cells / Q000378:metabolism; D004187:Disaccharides / Q000737:chemistry; D016220:Fibroblast Growth Factor 1 / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D005612:Freeze Drying; D006493:Heparin / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D013329:Structure-Activity Relationship; D013431:Sulfates / Q000378:metabolism*; D014574:Uronic Acids / Q000378:metabolism*
D002704:Chlorates; D004187:Disaccharides; D013431:Sulfates; D014574:Uronic Acids; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; D006493:Heparin