Effects of flavonoids on enzyme secretion and endocytosis in normal and mucolipidosis II fibroblasts

Abstract

The effect of flavonoids on β-hexosaminidase transport and endocytosis has been studied in cultured human skin fibroblasts. In mucolipidosis II fibroblast cultures, characterized by their preferential secretion of most newly synthesized hydrolases, quercetin and phloretin (200 μM) inhibited β-hexosaminidase synthesis as well as total culture-associated enzyme activity. Taxifolin induced a 2.4-fold increase in the total enzyme activity without altering the intra- and extra- cellular distribution of the enzyme. Rutin, although less effective, also stimulated an overall increase in total enzyme. The flavonoid effects were all concentration-dependent. Very little effect was observed in either the distribution or the total β-hexosaminidase activity in normal fibroblast cultures. Taxifolin and hesperitin inhibited receptor-mediated endocytosis of β-hexosaminidase by fibroblasts up to 50% of control uptake. Naringin, quercetin, and phloretin moderately inhibited uptake by 30% while rutin and fisetin had no effect. The results demonstrate that certain naturally occurring flavonoids affect the secretion of lysosomal enzymes as well as their endocytosis by fibroblasts. Since most individuals ingest up to one gram per day of these substances, flavonoids may prove to have significant effects on normal lysosomal enzyme physiology.