A study of the low β-galactosidase activity in cystinotic fibroblasts: effects of cysteamine

Abstract

β-Galactosidase activity but not β-glucuronidase, N- acetyl-β- d- galactosaminidase or arylsulphatase A activity, is known to be significantly lower in cultured human skin fibroblasts from patients with cystinosis than in cells from control subjects. Incubation of cell homogenates with disulphide or thiol compounds did not affect β-galactosidase activity, suggesting that decreased β-galactosidase activity in affected cells was not caused by the presence of inhibiting substances or absence of activating substances. Incubating cells with 0.5 or 1.0 mmol/1 cysteamine, a substance used in the clinical treatment of cystinosis because it depletes cells of excess cystine, greatly decreased β-galactosidase activity in both cystinotic and normal cells. This effect is shown to result from enzyme instability in lysosomes with raised pH and increased thiol concentration. Thus, cysteamine, although effective in depleting cystinotic cells of excess cystine, may have the undesired side-effect of severely decreasing lysosomal β-galactosidase.