Destabilization, oligomerization and inhibition of the mitogenic activity of acidic fibroblast-growth factor by aurintricarboxylic acid.
The triphenylmethane derivative aurintricarboxylic acid has been used to inhibit angiogenesis, vascular smooth muscle cell proliferation and cell transformation, an effect that has been attributed to its relatively nonspecific inhibitory activity of protein-nucleic acid interactions. Here, we show that this compound binds to acidic fibroblast growth factor, a prototypic member of a family of protein mitogens activated by heparin, altering its physicochemical properties and decreasing its mitogenic activity. Counteraction of the effects of aurintricarboxylic acid by heparin shows that the two compounds have opposite and reversible effects on acidic fibroblast growth factor structure and biological activity. The studies reported here may contribute to a deeper understanding of the inhibition of fibroblast-growth-factor-dependent mitogenesis of relevance to future pharmacologic developments.
Lozano
R M
RM
Departamento de Estructura y Función de Proteínas, Centro de Investigaciones Biológicas (C.S.I.C.), Madrid, Spain.
Rivas
G
G
Giménez-Gallego
G
G
D016475:3T3 Cells; D000818:Animals; D001312:Aurintricarboxylic Acid / Q000737:chemistry / Q000494:pharmacology*; D002942:Circular Dichroism; D004355:Drug Stability; D016220:Fibroblast Growth Factor 1 / Q000737:chemistry* / Q000187:drug effects* / Q000494:pharmacology; D006801:Humans; D046911:Macromolecular Substances; D051379:Mice; D008934:Mitogens / Q000494:pharmacology; D011487:Protein Conformation / Q000187:drug effects; D013050:Spectrometry, Fluorescence; D014461:Ultracentrifugation
D046911:Macromolecular Substances; D008934:Mitogens; D016220:Fibroblast Growth Factor 1; D001312:Aurintricarboxylic Acid