Accumulation of cholesterol and GM2 ganglioside in cells cultured in the presence of progesterone: an implication for the basic defect in Niemann-Pick disease type C.

Abstract Cultured fibroblasts from patients with Niemann-Pick disease type C (NP-C) are characterized by lysosomal accumulation of unesterified cholesterol and a defect in intracellular trafficking of cholesterol. We have found the accumulation of G M2 ganglioside in NP-C fibroblasts [Yano T, Taniguchi M, Akaboshi S, Vanier MT, Tai T, Sakuraba H, et al. Proc Japan Acad 1996;72B:214–219]. In this communication we show that several inhibitors known to inhibit intracellular cholesterol transport, progesterone, imipramine and KN-62, elicit accumulation of not only unesterified cholesterol but also G M2 ganglioside. This finding suggests that intracellular transport of cholesterol may be coupled with that of G M2 ganglioside. The accumulation of free cholesterol and G M2 ganglioside may be a clue for understanding the basic defect of NP-C. Recently NPC1 gene is found by the positional cloning. The mechanism of accumulating of G M2 ganglioside should be further investigated by studying of the functions of NPC1 gene.