ACCUMULATION OF CHOLESTEROL AND G(M2) GANGLIOSIDE IN CELLS CULTURED IN THE PRESENCE OF PROGESTERONE - AN IMPLICATION FOR THE BASIC DEFECT IN NIEMANN-PICK-DISEASE TYPE-C

Cultured fibroblasts from patients with Niemann-Pick disease type C (N P-C) are characterized by lysosomal accumulation of unesterified chole sterol and a defect in intracellular trafficking of cholesterol. We ha ve found the accumulation of G(M2) ganglioside in NP-C fibroblasts [Ya no T, Taniguchi M, Akaboshi S, Vanier MT, Tai T, Sakuraba H, et al. Pr oc Japan Acad 1996;72B:214-219]. In this communication we show that se veral 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 sugg ests that intracellular transport of cholesterol may be coupled with t hat of G(M2) ganglioside. The accumulation of free cholesterol and G(M 2) ganglioside may be a clue for understanding the basic defect of NP- C. Recently NPCI gene is found by the positional cloning. The mechanis m of accumulating of G(M2) ganglioside should be further investigated by studying of the functions of NPCI gene. (C) 1998 Elsevier Science B .V.