RECEPTOR-MEDIATED ENDOCYTOSIS OF A MANGANESE COMPLEX OF TRANSFERRIN INTO NEUROBLASTOMA (SHSY5Y) CELLS IN CULTURE

Exposure to manganese compounds often occurs as the result of industri al production or mining. Although manganese appears in traces in anima l and human tissue and is essential to certain biological processes, i t is also toxic. In humans and animals, toxicity is mainly associated with the nervous system. The mechanism underlying behavioral and bioch emical alterations observed after manganese intoxication is not fully understood. We have shown that the manganese present in serum after ex posure to manganese oxide is bound to transferrin as trivalent mangani c ion. In this study of manganese uptake and storage we used a clone o f human neuroblastoma cells (SHSY5Y). These cells differentiate and ex press catecholaminergic properties. Saturation binding analysis of the transferrin-manganese complex to the cells revealed a single class of binding sites, with an apparent K(D) of 13 +/- 1 nM and a density of 11,000 +/- 2,000 binding sites per cell. The complex was internalized in a temperature-dependent way and reached saturation after 2 h when a pproximately 2% of the added manganese had been internalized. About 80 % of the internalized manganese was found in ferritin after 24 h of ex posure. The results demonstrate that the transferrin receptor on SHSY5 Y cells can bind and internalize a manganese-transferrin complex as ef ficiently as an iron-transferrin complex, although a saturation of the manganese uptake was achieved.