Complementation, Cross Correction, and Drug Correction Studies of Combined β-Galactosidase Neuraminidase Deficiency in Human Fibroblasts

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Abstract
Summary: Neuraminidase activity in fibroblasts obtained from a patient with combined β-galactosidase-neuraminidase deficiency (β-gal−/neur−) was partially restored by fusion with two ML I cell lines and an ML II cell line. As observed with neuraminidase activity, β-galactosidase also showed complementation with an increase in activity when β-gal−/neur− fibroblasts were fused with an ML II or a GHi gangliosidosis cell line. Both GM, gangliosidosis and sialidosis fibroblasts secreted a “corrective factor” which, when added to medium above β-gal−/neur− fibroblasts, was pinocytosed and partially corrected its deficiencies for these two enzymes.This partial correction of β-galactosidase and neuraminidase activities persisted for at least 72 h after removal of the “corrective factor” from the medium. A “corrective factor” with similar properties was obtained from glycoproteins isolated by chromatography of human spleen homogenates on concanavalin A-Sepharose. Treatment of-β-gal−/neur− fibroblasts with leupeptin or EP475, two inhibitors of lysosomal thiolproteases, partially restored β-galactosidase activity but caused no significant improvement in neuraminidase levels. The partial corrective effect of leupeptin on partial corrective effect of leupeptin on β-galactosidase activity persisted for at least 2 d after removal of the drug, even in the presence of cycloheximide.-galactosidase activity persisted for at least 2 d after removal of the drug, even in the presence of cycloheximide.