Lysosomal glycosphingolipid storage in chloroquine-induced alpha-galactosidase-deficient human endothelial cells with transformation by simian virus 40: in vitro model of Fabry disease.
Human umbilical venous endothelial cells were transformed with a temperature-sensitive mutant of simian virus 40, tsA640, and a cell line, subcultured for over 20 serial passages, was established at a temperature permissive for the virus. Treatment of transformed endothelium with 3 micrograms/ml chloroquine caused a specific reduction of alpha-galactosidase activity, without cell injury, and revealed several electron-dense materials surrounded by single unit membranes. Crystalline lamellae in lysosomes with a periodicity of 6.5 nm, which are typically seen in various tissues in Fabry disease, were produced in the presence of a glycosphingolipid mixture. These cells should be useful for in vitro pathophysiological studies on Fabry endothelium.
Inagaki
M
M
Division of Child Neurology, Faculty of Medicine, Tottori University, Yonago, Japan.
Katsumoto
T
T
Nanba
E
E
Ohno
K
K
Suehiro
S
S
Takeshita
K
K
D002472:Cell Transformation, Viral; D002738:Chloroquine / Q000494:pharmacology*; D002997:Clomipramine / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D000795:Fabry Disease / Q000473:pathology*; D005696:Galactosidases / Q000172:deficiency*; D006028:Glycosphingolipids / Q000378:metabolism*; D006801:Humans; D008247:Lysosomes / Q000378:metabolism*; D008854:Microscopy, Electron; D013539:Simian virus 40 / Q000502:physiology; D014299:Trimipramine / Q000494:pharmacology
D006028:Glycosphingolipids; D014299:Trimipramine; D002738:Chloroquine; D005696:Galactosidases; D002997:Clomipramine