The effects of psychosine upon growth of human skin fibroblasts from patients with globoid cell leukodystrophy.
[3H]Thymidine incorporation into cultured skin fibroblasts from patients with globoid cell leukodystrophy (GLD) and from control individuals was utilized to monitor the effects of psychosine (galactosylsphingosine) upon cell replication. The concentration of psychosine necessary to inhibit 50% (ID50) of the growth of cultured skin fibroblasts was approximately 15 microgram/ml for both normal and GLD fibroblasts deficient in the enzyme galactosylceramide beta-galactosidase. Growth inhibition curves for GLD and for control fibroblasts were comparable after 3 days and after 7 days exposure to the glycolipid, so that accumulation of psychosine was not a critical factor affecting toxicity. Galactosylceramide, the major substrate for the enzyme galactosylceramide beta-galactosidase, did not inhibit [3H]thymidine incorporation into either normal or GLD fibroblasts at the concentration tested, in contrast to the highly toxic effects of psychosine at similar concentrations. The comparable inhibitory levels of psychosine in control cells and in GLD fibroblasts which are deficient in ability to hydrolyze this glycolipid suggest that the toxicity of psychosine is nonspecific. Therefore, these results are not consistent with the concept that globoid cell leukodystrophy is primarily a psychosine lipidosis.
D000328:Adult; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000201:enzymology; D005698:Galactosylceramidase / Q000378:metabolism; D006801:Humans; D007965:Leukodystrophy, Globoid Cell / Q000201:enzymology*; D008297:Male; D008938:Mitosis / Q000187:drug effects; D011609:Psychosine / Q000494:pharmacology*; D013110:Sphingosine / Q000031:analogs & derivatives*; D013936:Thymidine / Q000378:metabolism
D011609:Psychosine; D005698:Galactosylceramidase; D013110:Sphingosine; D013936:Thymidine