EFFECTS OF DRUGS ON CHOLESTEROL ESTERIFICATION IN NORMAL AND NIEMANN-PICK TYPE-C FIBROBLASTS - AY-9944, OTHER CATIONIC AMPHIPHILIC DRUGS AND DMSO

被引：21

作者：

YOSHIKAWA, H ^{[1
]}

机构：

[1] NATL CTR NEUROL & PSYCHIAT,NATL INST NEUROSCI,DIV INHERITED METAB DISORDERS,KODAIRA,TOKYO 187,JAPAN

来源：

BRAIN & DEVELOPMENT | 1991年 / 13卷 / 02期

关键词：

NIEMANN-PICK DISEASE TYPE-C; CHOLESTEROL ESTERIFICATION; CATIONIC AMPHIPHILIC DRUG; AY-9944; DIMETHYLSULFOXIDE;

D O I：

10.1016/S0387-7604(12)80118-5

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

AY-9944 and other amphiphilic drugs (CADs) have been reported to cause a reduction of acid sphingomyelinase activity in fibroblasts and various tissues in the rat, and DMSO has been known to correct a partial deficiency of acid sphingomyelinase activity in Niemann-Pick type C (NPC) fibroblasts. Furthermore, in the present study we demonstrated that AY-9944 and other CADs caused a marked reduction of cholesterol esterification in control fibroblasts and an excessive intracellular accumulation of unesterified cholesterol as in NPC cells, and that this reduction could partially be corrected by the addition of 2% DMSO to the medium. These characteristics of the drug-treated cells mimick the phenomena seen in NPC fibroblasts. Therefore, fibroblasts treated with CADs may be used as a model of drug-induced lipidosis of NPC. The effect of DMSO suggests the possibility of its usefulness in the treatment of NPC patients.

引用

页码：115 / 120

页数：6

共 22 条

[1] LIPID AND LYSOSOMAL-ENZYMES IN HUMAN-FIBROBLASTS CULTURED WITH PERHEXILINE-MALEATE [J].