Inhibition of β-Glucosidase by N-(n-Hexyl)-O-glucosylsphingosine in Cell Strains of Neurological Origin

摘要: Abstract N-(n-Hexyl)-O-glucosylsphingosine completely inhibited β-glucosidase in cultured rat astrocytoma (RGC-6) and mouse neuroblastoma cell strains (NB41A NB2a), creating a model for the infantile Gaucher nervous system. The inhibitor, at concentration of 5 µg per ml, caused 5-fold elevation glucosylceramide RGC-6 6-fold NB41A cells. Under these conditions growth rates cells were unaffected. Other lysosomal enzymes only depressed to approximately 80% normal with exception β-glucuronidase (37% normal); such reductions would not be anticipated cause abnormal pathology none was observed. Studies glucosyl[14C]ceramide (labeled stearoyl moiety) showed that glycolipid rapidly taken up from medium. In presence inhibitor uptake reduced NB2a, NB41A, cells, latter two no subsequent catabolism could detected. more complex glycolipids, as gangliosides, they readily metabolized affected by inhibitor. This interpreted evidence β-glucosidases, one which utilizes free is deficient Gaucher's disease other acts an integral part multienzyme degradation glycolipids has activity disease. Results indicated specific catabolic reactions may substrate analogs simulate certain genetic diseases neurons glia tissue culture.